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Objective To understand the application of skin disinfectant in neonatal intensive care units(NICUs)nationwide.Methods From April to May 2023,application of skin disinfectant in 93 NICUs nationwide was sur-veyed with convenience sampling method by a self-designed questionnaire.Questionnaire contents included types of disinfectant,disinfection tools,cleaning and disinfection frequency,disinfectant drying status,removal of disinfec-tant,and adverse reactions caused by disinfectant.Results A total of 93 nursing units in 71 medical institutions from 25 provinces/municipalities were included in this study.In NICUs,three most commonly used disinfectants were ethanol(79.57％),iodophor(74.19％),and anerdian(62.37％).In nursing units for neonates＜2 months of age,chlorhexidine was prohibited in 28 units(30.11％),used with caution in 23 units(24.73％),allowed in 9 units(9.68％),and there was no unified requirement in 33 units(35.48％).When using ethanol,staff only wiped once in 13(17.57％)nursing units.In some nursing units,there was no unified requirements on the wiping fre-quency of disinfectant.As for the removal of residual iodine,saline was used in 29(42.03％)nursing units,ethanol in 8(11.59％),and 19(27.54％)did not have unified requirements.The adverse reactions of disinfectant mainly included rash and contact dermatitis.Disinfectants that caused adverse reactions included ethanol,iodophor,aner-dian,and chlorhexidine.Conclusion In clinical practice,unified standards for the use of neonatal skin disinfectant remain absent.Selection and use of neonatal skin disinfectant vary considerably.Neonatal skin disinfectants have common adverse reactions.It is necessary to strengthen the training of health care workers on the standardized use of disinfectant,as well as carry out large-scale and rigorous randomized controlled trial designs to provide scientific basis for the correct selection of disinfectant.
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Magnetic cell sorting technology is a highly specific and rapid cell sorting technology using superparamagnetic nanocomposites for cell sorting, which is widely used in immunology, stem cytology, oncology, clinical medicine and other fields. Magnetic cell sorting technology is divided into positive isolation, negative isolation/untouched cell isolation, depletion, multi-step isolation and automated cell separation systems. In this review, we firstly give a brief introduction to the classification and application of magnetic cell sorting technology, then discuss several new techniques and challenges based on magnetic cell sorting in recent years, such as improving the sorting efficiency by improving the structure of magnetic materials and magnetic field structure. The necessity of biological evaluation of magnetic cell sorting products was emphatically analyzed. Through the biological evaluation, the advantages and disadvantages of magnetic cell sorting products can be understood, and the research and development ability could be improved. Therefore, 10 biological evaluation technical parameters related to magnetic cell sorting products were proposed: yield, purity, sterility, cytotoxicity, cell morphology, viability, light scattering characteristics of cells, fluorescent antibody labeling ability of cells, cell activation and cell proliferation. The 10 biological evaluation technical parameters play an important role in promoting the standardized application of magnetic cell sorting.
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Thirty-one phenolic constituents were isolated and purified from the 95% ethanol extract of Sanguisorbae Radix by using various chromatographic techniques, including macroporous resin, silica gel, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated by physicochemical properties, spectroscopic data (MS and NMR) and electronic circular dichroism (ECD) spectra, and identified as 3-methoxyl-2S,3S-epoxyflavanone (1a), 3-methoxyl-2R,3R-epoxyflavanone (1b), longifoin B (2), longifoin C (3), eriodictyol (4), naringenin (5), liquiritigenin (6), 5,3ʹ-dihydroxy-7,4ʹ-dimethoxyflavanone (7), naringenin-7-O-β-D-glucopyranoside (8), dihydroquercetin (9), dihydrokaempferol (10), (-)-garbanzol (11), (2R,3R)-4-methoxyl-distylin (12), kaempferol (13), quercetin (14), α,4,2′,4′-tetrahydroxydihydrochalcone (15), phloretin (16), (+)-catechin (17), ethyl (+)-cyanidan-3-ol-8-carboxylate (18), phyllocoumarin (19), methyl 3-methoxy-4,5-dihydroxybenzoate (20), 4,5-dimethoxy-3-hydroxybenzoic acid methyl ester (21), 3,4′-di-O-methylellagic acid (22), 3,4,3′-O-trimethylellagic acid (23), 3,3ʹ,4ʹ-O-trimethylellagic acid-4-O-β-D-xyloside (24), (3R)-thunberginol C (25), resveratrol (26), 1-hydroxypinoresinol (27), (7S,8S)-3-methoxy-3′,7-epoxy-8,4′-oxyneoligna-4,9,9′-triol (28), emodin-8-O-β-D-glucoside (29), phloracetophenone (30) and 4-(4′-hydroxyphenyl)-butan-2-one (31). Among them, compound 1a and 1b is a pair of new flavonoid enantiomers, compounds 2 and 3 are a pair of new epimers, while compounds 4, 5, 6, 9, 10, 13, 16 and 26 were obtained from S. officinalis for the first time, compounds 7, 8, 27, 30 and 31 were isolated for the first time from the S. officinalis genus, and compounds 11, 12, 15, 18, 19, 25, 28 and 29 were isolated for the first time from the Rosaceae. The antioxidant activities of compounds 1-24 were evaluated by activating the Nrf2 transcriptional pathway, which were measured by the dual-luciferase reporter gene assay in 293T cells. Compounds 4, 6-10, 12, 14, 17, 19, 20 and 22-24 showed significant Nrf2 agonistic effect compared with the control group at 25 μmol·L-1, which provided reference for the research of their antioxidant activity.
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A new Schiff base modified MCM-41 molecular sieve(N-MCM-41)was synthesized via post-grafting method with 2-pyridine formaldehyde for efficient removal of lead ions(Pb2+)from aqueous solution.X-ray diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM),Fourier transform-infrared(FT-IR)spectroscopy,thermogravimetric analysis(TGA),and X-ray photoelectron spectroscopy(XPS)were employed to characterize the structure,morphology,surface functional groups and chemical states of N-MCM-41.Moreover,the adsorption behavior of Pb2+by N-MCM-41 was systematically studied.Batch adsorption studies revealed that N-MCM-41 showed the maximal adsorption capacity of 101.3 mg/g at 45℃and pH=5.5 under the initial Pb2+ concentration of 80 mg/L after 180 min adsorption.The adsorption process conformed to the Langmuir isotherm model and the pseudo-second-order kinetics model.The adsorption of Pb2+by N-MCM-41 was a spontaneous and endothermic process.Adsorption mechanism analyses suggested that functional groups on N-MCM-41 had strong coordination ability with Pb2+to improve the adsorption capacity.The synthesized N-MCM-41 adsorbent exhibited excellent reusability in five regeneration cycles.Overall,this study showed that the N-MCM-41 had good application prospect to remove Pb2+ from aqueous solution.
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Objective To investigate the distribution of traditional Chinese medicine(TCM)constitution in pregnant women with iron deficiency anemia(IDA)and its related influencing factors,so as to provide a reference for the TCM prevention and treatment of IDA in pregnancy.Methods A total of 109 eligible patients with IDA during pregnancy were included in the study.The general data of pregnant women,the TCM constitution types and relevant laboratory indicators including serum ferritin(Fer),hemoglobin(Hb)and mean corpuscular volume(MCV)were collected.Statistical analyses were conducted on the distribution of TCM constitution types of IDA pregnant women and its related influencing factors as well as the pregnancy outcomes.Results(1)The 109 IDA pregnant women were predominated by biased constitution types,accounted for 60 cases(55.05％).The distribution of the constitution types of 109 IDA pregnant women was as follows:balanced constitution(49 cases,44.95％)>damp-heat constitution(13 cases,11.93％)>yang deficiency constitution(12 cases,11.01％)>yin deficiency constitution(11 cases,10.09％)>qi deficiency constitution(10 cases,9.17％)>qi stagnation constitution(9 cases,8.26％)>blood stasis constitution(3 cases,2.75％)>phlegm-damp constitution(2 cases,1.83％).(2)Comparison of Hb and MCV levels in IDA pregnant women with various constitution types showed no statistically significant differences(P>0.05),but Fer level in IDA pregnant women with damp-heat constitution was significantly higher than that in IDA pregnant women with balanced constitution(P<0.01),and the probability of occurrence of amniotic opacity in IDA pregnant women with damp-heat constitution was significantly higher than that in IDA pregnant women with balanced constitution and other biased constitution types(P<0.05).Conclusion Damp-heat constitution is the most common TCM constitution type in pregnant women with IDA,followed by yang deficiency constitution,yin deficiency constitution and qi deficiency constitution.The damp-heat constitution may be the susceptible constitution of pregnant women with IDA,and IDA pregnant women with damp-heat constitution have significantly higher Fer level than those with balanced constitution,and also have the higher probability of occurrence of amniotic opacity than those with balanced constitution and other biased constitution types.
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Objective To compare paired boxed gene 1(PAX1)methylation and p16/Ki-67 double staining alone and in combination in thinprep cytologic test(TCT)for distinguishing atypical squamous cells of undetermined significance(ASC-US)and low-grade squamous intraepithelial lesion(LSIL)population.Methods A total of 247 patients with TCT results of ASC-US and LSIL admitted in our hospital from January 2021 to December 2022 were enrolled in this study.Detection efficacy of PAX1 methylation and p16/Ki-67 double staining alone and in combination was evaluated with colposcopic pathologic results as the gold standard and the sensitivity,specificity,accuracy and area under the curve(AUC)as evaluation indexes.Results The positive rates of PAX1 methylation and p16/Ki-67 double staining were increased with the severity of pathological findings.Combined detection of PAX1 methylation and p16/Ki-67 assay had a sensitivity of 91.25％,specificity of 97.72％and accuracy of 95.51％in the women with TCT of ASC-US,and these values were statistically better than those of PAX1 methylation and p16/Ki-67 double staining alone(P＜0.01).Conclusion The combination of PAX1 methylation and p16/Ki-67 double-staining assay can further improve the diagnostic efficacy in patients with ASC-US on TCT results.
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Objective To investigate the effects of methionine restriction(MR)on macrophages in lipopolysaccharide(LPS)-induced acute lung injury(ALI)and to explore the underlying mechanism.Methods According to the random number table method,36 male C57BL/6J mice(6～8 weeks old,23±2 g)were divided into 3 groups with 12 mice in each group:the sham group,the LPS group and the LPS+MR group.HE staining and pathological scoring of lung injury were performed in lung tissues.The expression of LPS-binding protein(LBP)and Toll-like receptor-4(TLR4)was detected by RT-qPCR and Western blotting.Macrophage-colony stimulating factor(M-CSF),granulocyte-macrophage-colony stimulating factor(GM-CSF)and chemokine C-C motif ligand 3(CCL3)which are all macrophage-associated chemokines were analyzed by immunohistochemistry.Results Compared with the sham group,the pathological score of lung injury in the LPS group was significantly increased(P＜0.01);The mRNA and protein expression levels of LBP and TLR4 were significantly increased;The number of positive cells of CD11b,F4/80,M-CSF,GM-CSF and CCL3 were significantly increased(P＜0.01).MR significantly improved LPS-induced ALI,and decreased the pathological score of lung injury(P＜0.01);The mRNA and protein expression levels of LBP and TLR4 were decreased;Compared with the LPS group,the number of positive cells of CD11 b,F4/80,M-CSF,GM-CSF and CCL3 were reduced in the LPS+MR group(P＜0.01).Conclusion MR could attenuate LPS-induced ALI by inhibiting the expression of macrophage chemokines and preventing infiltration and activation of macrophage to lungs.
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The solute carrier family 4 (SLC4) includes 10 members (SLC4A1-5, SLC4A7-11), which are expressed in multiple tissues in the human body. The SLC4 family members differ in their substrate dependence, charge transport stoichiometry and tissue expression. Their common function is responsible for the transmembrane exchange of multiple ions, which is involved in many important physiological processes, such as erythrocyte CO2 transport and the regulation of cell volume and intracellular pH. In recent years, many studies have focused on the role of SLC4 family members in the occurrence of human diseases. When SLC4 family members have gene mutations, a series of functional disorders will occur in the body, leading to the occurrence of some diseases. This review summarizes the recent progress about the structures, functions and disease correlation of SLC4 members, in order to provide clues for the prevention and treatment of related human diseases.
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Humans , Mutation , SLC4A Proteins/physiologyABSTRACT
Objective To investigate the incidence rate of pulmonary infection after laparoscopic surgery and related risk factors in patients with hepatocellular carcinoma (HCC) comorbid with liver cirrhosis and portal hypertension (PHT). Methods A retrospective analysis was performed for the clinical data of 105 HCC patients with liver cirrhosis and PHT who underwent laparoscopic surgery in Beijing Ditan Hospital, Capital Medical University, from January 2017 to February 2022. A total of 30 factors that might cause pulmonary infection were recorded, including general information, disease factors, surgical factors, and postoperative factors. Postoperative recovery was observed and the occurrence of pulmonary infection was recorded. The chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups, and the multivariate logistic regression analysis was used to investigate the independent risk factors for pulmonary infection. Results Among the 105 patients, 66 underwent laparoscopic devascularization combined with hepatectomy and 39 underwent laparoscopic devascularization combined with radiofrequency ablation (RFA). The surgery was successful for all patients, with no case of conversion to laparotomy or unscheduled reoperation. No death was observed within 30 days after surgery and during hospitalization, with a median length of hospital stay of 20 days (range 14-25 days). The incidence rate of pulmonary infection was 25.71% (27/105). Smoking (odds ratio [ OR ]=3.362, 95% confidence interval [ CI ]: 1.282-8.817, P =0.014), MELD score ( OR =3.801, 95% CI : 1.007-14.351, P =0.049), tumor location ( OR =1.937, 95% CI : 1.169-3.211, P =0.010), surgical procedure ( OR =0.006, 95% CI : 0.001-0.064, P =0.000), intraoperative infusion volume ( OR =4.871, 95% CI : 1.211-19.597, P =0.026), and postoperative pleural effusion ( OR =9.790, 95% CI : 1.826-52.480, P =0.008) were independent risk factors for pulmonary infection. Conclusion There is a relatively high risk of pulmonary infection in HCC patients with liver cirrhosis and PHT undergoing laparoscopic surgery. Postoperative pleural effusion is the high risk factor for pulmonary infection, and devascularization combined with RFA can significantly reduce the risk of pulmonary infection. It is recommended to strengthen preoperative rehabilitation, perioperative liver function maintenance, intraoperative damage control, and goal-oriented fluid therapy and reduce postoperative fluid accumulation in the third space, so as to reduce the incidence rate of pulmonary infection.
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OBJECTIVE@#To evaluate the characteristics of severe periodontitis with various number of tooth loss during 4-year natural progression, and to analyze the factors related to higher rate of tooth loss.@*METHODS@#A total of 217 patients aged 15 to 44 years with severe periodontitis were included, who participated in a 4-year natural progression research. Data obtained from questionnaire survey, clinical examination and radiographic measurement. Tooth loss during 4-year natural progression was evaluated. The baseline periodontal disease related and caries related factors were calculated, including number of teeth with bone loss > 50%, number of missing molars, number of teeth with widened periodontal ligament space (WPDL), number of teeth with periapical lesions and etc. Characteristics of populations with various number of tooth loss and the related factors that affected higher rate of tooth loss were analyzed.@*RESULTS@#In 4 years of natural progression, 103 teeth were lost, and annual tooth loss per person was 0.12±0.38. Nine patients lost 3 or more teeth. Thirty-four patients lost 1 or 2 teeth, and 174 patients were absent of tooth loss. Molars were mostly frequent to lose, and canines presented a minimum loss. The number of teeth with WPDL, with periapical lesions, with intrabony defects, with probing depth (PD)≥7 mm, with PD≥5 mm, with clinical attachment loss≥5 mm, with bone loss > 50% and with bone loss > 65% were positively correlated to number of tooth loss. Results from orderly multivariate Logistic regression showd that the number of teeth with bone loss > 50% OR=1.550), baseline number of molars lost (OR=1.774), number of teeth with WPDL (1 to 2: OR=1.415; ≥3: OR=13.105), number of teeth with periapical lesions (1 to 2: OR=4.393; ≥3: OR=9.526) and number of teeth with caries/residual roots (OR=3.028) were significant risk factors related to higher likelihood of tooth loss and multiple tooth loss.@*CONCLUSION@#In 4 years of natural progression, the number of teeth with bone loss > 50%, baseline number of missing molars, number of teeth with WPDL, baseline number of teeth with periapical lesions and number of teeth with caries/residual roots were significantly related to higher risk of tooth loss and multiple tooth loss among Chinese young and middle-aged patients with severe periodontitis in rural areas.
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Humans , Tooth Loss/etiology , Periodontitis/complications , Tooth , Periodontal Diseases , MolarABSTRACT
Epigenetics refers to heritable changes in gene expression and function without alterations in gene sequences,including DNA methylation,histone modification,and non-coding RNAs.Endometriosis is a benign gynecological disease that affects the fertility and health of reproductive-age women,the etiology of which remains unclear.The recent studies have demonstrated that epigenetics plays a key role in the occurrence and development of endometriosis.This article reviews the research progress in the regulatory mechanism and application of epigenetics in endometriosis.
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Female , Humans , Endometriosis/genetics , Epigenesis, Genetic , DNA Methylation , Protein Processing, Post-TranslationalABSTRACT
Since Curcumae Radix decoction pieces have multiple sources, it is difficult to distinguish depending on traditional cha-racters, and the mixed use of multi-source Curcumae Radix will affect its clinical efficacy. Heracles Neo ultra-fast gas phase electronic nose was used in this study to quickly identify and analyze the odor components of 40 batches of Curcumae Radix samples from Sichuan, Zhejiang, and Guangxi. Based on the odor fingerprints established for Curcumae Radix decoction pieces of multiple sources, the odor components was identified and analyzed, and the chromatographic peaks were processed and analyzed to establish a rapid identification method. Principal component analysis(PCA), discriminant factor analysis(DFA), and soft independent modeling cluster analysis(SIMCA) were constructed for verification. At the same time, one-way analysis of variance(ANOVA) combined with variable importance in projection(VIP) was employed to screen out the odor components with P<0.05 and VIP>1, and 13 odor components such as β-caryophyllene and limonene were hypothesized as the odor differential markers of Curcumae Radix decoction pieces of diffe-rent sources. The results showed that Heracles Neo ultra-fast gas phase electronic nose can well analyze the odor characteristics and rapidly and accurately discriminate Curcumae Radix decoction pieces of different sources. It can be applied to the quality control(e.g., online detection) in the production of Curcumae Radix decoction pieces. This study provides a new method and idea for the rapid identification and quality control of Curcumae Radix decoction pieces.
Subject(s)
Drugs, Chinese Herbal/analysis , Electronic Nose , China , Plant Roots/chemistry , Limonene/analysis , Chromatography, High Pressure LiquidABSTRACT
Objective: To investigate the influence of light and heavy bite force on the mandibular movement trajectories, and the influence of bite force on virtual occlusal pre-adjustment of digital full crown. Methods: From October 2021 to March 2022, 10 postgraduate volunteers (3 males and 7 females, aged 22-26 years) were recruited from Peking University School and Hospital of Stomatology. Maxillary and mandibular digital models of the participants were obtained by intraoral scanning. Jaw relations were digitally transferred under heavy bite force and mandibular movement trajectories under light and heavy bite force were recorded by jaw motion analyser. Three mandibular markers were chosen, namely the mesial proximal contact point of the central incisor (incisal point) and the mesial buccal cusp tips of the bilateral first molars. The three-dimensional displacements of the markers under two kinds of bite force in the intercuspal position (ICP), the sagittal projection of the three-dimensional displacements in the protrusive edge-to-edge position, and the coronal projection of the three-dimensional displacements in the lateral edge-to-edge position of upper and lower posterior teeth were measured. Single-sample t-test was used to compare the three-dimensional displacements and the corresponding sagittal projection and coronal projection with 0, respectively. The left maxillary central incisor and left mandibular first molar were virtually prepared by the reverse engineering software. Then dental design software was used to design digital full crown using the copy method. The mandibular movement trajectories under light and heavy bite force were separately used to guide virtual occlusal pre-adjustment. The three-dimensional deviations (mean deviations and root mean square) between the lingual surface of the left maxillary central incisor or the occlusal surface of the left mandibular first molar and that of the natural tooth before preparation were calculated (light bite force group and heavy bite force group), and the differences between the two groups were compared by the paired t-test. Results: Under the two kinds of bite force, the three-dimensional displacements of the markers in the ICP were (0.217±0.135), (0.210±0.133) and (0.237±0.101) mm, respectively; the sagittal projection of the three-dimensional displacements of the markers in the protrusive edge-to-edge position were (0.204±0.133), (0.288±0.148) and (0.292±0.136) mm, respectively; the coronal projection of the three-dimensional displacements of the mesial buccal cusp tips of the bilateral first molars in the lateral edge-to-edge position were (0.254±0.140) and (0.295±0.190) mm, respectively. The differences between the above displacements and 0 were statistically significant (P<0.05). The results of occlusal pre-adjustment showed that the mean deviations of the lingual surface of the left maxillary central incisor in the light and heavy bite force groups were (0.215±0.036) and (0.195±0.041) mm (t=3.95, P=0.004), respectively. The mean deviations of the occlusal surface of the left mandibular first molar were (0.144±0.084) and (0.100±0.096) mm (t=0.84, P=0.036), respectively. Conclusions: Both the light and heavy bite force have an influence on the mandibular movement trajectories. Virtual occlusal pre-adjustment of prostheses with mandibular movement trajectories under heavy bite force can obtain morphology of lingual or occlusal surfaces closer to the natural teeth before preparation.
Subject(s)
Male , Female , Humans , Bite Force , Tooth , Mandible , Molar , Occlusal AdjustmentABSTRACT
Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Subject(s)
Humans , Middle Aged , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Immune Checkpoint Inhibitors/therapeutic use , Neoadjuvant Therapy , Prospective Studies , Rectal Neoplasms/pathology , Thrombocytopenia/drug therapy , Treatment OutcomeABSTRACT
Objective: To investigate whether tanshinone ⅡA can protect the apoptosis of mice cochlear pericytes induced by high glucose and its specific protective mechanism, so as to provide experimental evidence for the prevention and treatment of diabetic hearing loss. Methods: C57BL/6J male mice were used to prepare type 2 diabetes model, which were divided into normal (NG) group, diabetic (DM) group, diabetic+tanshinone ⅡA (HG+tanshinone ⅡA) group and tanshinone ⅡA group. Each group had 10 animals. Primary cochlear pericytes were divided into NG group, HG group (high glucose 35 mmol/L), HG+tanshinone ⅡA (1, 3, 5 μmol/L) group, HG+Tanshinone ⅡA+LY294002 (PI3K/AKT pathway inhibitor) group, LY294002 group, tanshinone ⅡA group and DMSO group. Auditory brainstem response (ABR) was used to measure hearing threshold. Evans blue was used to detect the permeability of blood labyrinth barrier in each group. TBA methods were used to detect oxidative stress levels in various organs of mice. Morphological changes of stria vascularis were observed by hematoxylin-eosin staining (HE). Evans blue was used to detect the vascular labyrinth barrier permeability in cochlea. The expression of apoptosis protein in stria vascularis pericytes was observed by immunofluorescence. Pericytes apoptosis rate was observed by flow cytometry. DCFH-DA was combined with flow cytometry to detect intracellular ROS content, and Western blot was used to detect the expression of apoptotic proteins (Cleaved-caspase3, Bax), anti-apoptotic proteins (BCL-2) and pathway proteins (PI3K, p-PI3K, AKT, p-AKT). SPSS software was used for statistical analysis. Independent sample t test was performed, and P<0.05 was considered statistically significant. Results: Animal experiments: Tanshinone ⅡA decreased the hearing threshold of DM group [(35.0±3.5) dB SPL vs. (55.3±8.1) dB SPL] (t=4.899, P<0.01), decreased the oxidative stress level in cochlea (t=4.384, P<0.05), improved the structure disorder, atrophy of cochlea vascular lines, vacuole increased phenomenon. Tanshinone ⅡA alleviated the increased permeability of the blood labyrinth barrier [Evans blue leakage (6.84±0.27) AU vs. (8.59±0.85) AU] in the cochlea of DM mice (t=2.770, P<0.05), reversed the apoptotic protein: Caspase3 (t=4.956, P<0.01) and Bax (t=4.388, P<0.05) in cochlear vascularis. Cell experiments: Tanshinone ⅡA decreased intracellular ROS content in a concentration-dependent way (t=3.569, P<0.05; t=4.772, P<0.01; t=7.494, P<0.01); Tanshinone ⅡA decreased apoptosis rate and apoptotic protein, and increased the expression of anti-apoptotic protein, p-PI3K/PI3K and p-AKT/AKT in concentration-dependent manner (all P values<0.05); LY294002 reversed the protective effect of tanshinone ⅡA on pericytes apoptosis (all P values<0.05). Conclusion: Tanshinone ⅡA can inhibit the apoptosis of cochlear pericytes induced by high glucose by reducing oxidative stress level and activating PI3K/AKT signaling pathway under high glucose environment, thus playing a protective role in diabetic hearing loss.
Subject(s)
Animals , Male , Mice , Apoptosis , bcl-2-Associated X Protein , Diabetes Mellitus, Type 2 , Evans Blue , Glucose , Hearing Loss , Mice, Inbred C57BL , Pericytes/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Signal TransductionABSTRACT
Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.
Subject(s)
Male , Adult , Humans , Aged , Lymphoma, Mantle-Cell/drug therapy , Prognosis , Retrospective Studies , Bone Marrow/pathology , Risk FactorsABSTRACT
Objective:To study the risk factors of early postoperative portal vein thrombosis (PVT) after salvage devascularization for failed endoscopic therapy.Methods:A retrospective analysis was conducted on the clinical data of 525 cirrhotic patients who underwent pericardial devascularization for portal hypertension and esophagogastric variceal bleeding at the Department of General Surgery, Beijing Ditan Hospital, Capital Medical University from January 2012 to January 2022. There were 435 males and 90 females, aged 47(37, 58) years old. These patients were divided into two groups based on whether PVT occurred after devascularization: the PVT group ( n=225) and the non-PVT group ( n=300). Clinical data including gender, age, portal vein diameter and postoperative platelet elevation level (PPEL) were studied and the related factors of PVT were analyzed by univariate analysis. Factors with statistically significant differences were included in logistic regression analysis. Results:Univariate analysis showed that the significant risk factors of PVT were the scores of the model of end-stage liver disease, platelets, portal vein diameter, endoscopic therapy, operation duration, surgical bleeding volume, intraoperative blood transfusion and PPEL on the first and third postoperative days (all P<0.05). Multivariate analysis showed that portal vein diameter ≥13 mm ( OR=6.000, 95% CI: 3.418-10.533), endoscopic injection ( OR=1.894, 95% CI: 1.196-2.998), operation duration ≥ 180 min ( OR=8.520, 95% CI: 5.333-13.554), PPEL ≥ 20×10 9/L on the first postoperative day ( OR=2.125, 95% CI: 1.306-3.456) and PPEL≥50×10 9/L on the third postoperative day ( OR=1.925, 95% CI: 1.192-3.109) increased the risk of PVT (all P<0.05). Conclusion:The diameter of portal vein, endoscopic treatment, operation duration and PPEL on the first and third days after operation were independent risk factors of early postoperative PVT development.
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Objective To evaluate the effect of targeted monitoring and multi-modular improvement strategy on the prevention and control of catheter-associated urinary tract infection(CAUTI).Methods Patients with indwe-lling urinary catheter in a tertiary first-class hospital from January 2018 to December 2022 were selected as the re-search subjects.Targeted monitoring results and distribution of pathogenic bacteria in 5 consecutive years were ana-lyzed,and a multi-modular improvement strategy based on the targeted monitoring results was implemented.The occurrence of CAUTI before and after implementation,status and effectiveness of training in prevention and control measures were compared respectively.Results Before and after the implementation of the multi-modular improve-ment strategy,health care workers'compliance rate of hand hygiene,awareness rate of prevention and control measures,and implementation rate of prevention and control measures all increased significantly(all P＜0.001).Targeted monitoring results showed that daily test rates of urine culture and routine urine from patients with in-dwelling catheters have been on the rise in 5 consecutive years(P＜0.05).A total of 397 cases of CAUTI occurred in the past 5 years.Incidences of CAUTI in general intensive care unit(ICU)and surgical ICU showed decreasing trends in 5 consecutive years(all P＜0.05).Incidence of CAUTI in general wards showed no statistically significant difference in 5 years(P=0.088).A total of 431 strains of pathogenic bacteria were detected,mainly Gram-negative bacteria.Daily incidence of multidrug-resistant organism infection in patients with indwelling catheters was 0.12‰.After the implementation of the multi-modular improvement strategy,incidence of CAUTI in all departments re-duced significantly(P＜0.05).Conclusion Targeted monitoring can help identify departments with high-risk of CAUTI,multi-modular improvement strategy can raise the quality of prevention and control of CAUTI in all occa-sions,reduce the incidence of CAUTI,and is worthy of clinical promotion and application.
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The obstacles and risks of the application of imaging devices such as CT,PET/CT,MRI and in vivo imaging system in animal biosafety level 3/4(ABSL-3/4)laboratories were proposed.Combined with the experience of applying imaging devices in ABSL-3/4 laboratories,the key issues were discussed such as application scheme,risk assessment and control,disinfection and sterilization methods.Some suggestions were put forward for applying large-scale imaging equipment in ABSL-3/4 laboratories.References were provided for ABSL-3/4 laboratories equipped with imaging devices.[Chinese Medical Equipment Journal,2023,44(9):69-73]
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The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.