[Effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix in the treatment of children with deep burns].

Objective: To explore the effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix (ADM), i.e., early surgery, in the treatment of children with deep burns. Methods: This study was a retrospective cohort study. From January 2017 to December 2022, 278 deep burned hospitalized children aged 1-7 years who met the inclusion criteria were admitted to Central Hospital Affiliated to Shandong First Medical University. According to the differences in treatment processes, 134 children who underwent early surgery+routine dressing change were enrolled in eschar removal+dressing change group (77 males and 57 females, aged 1 (1, 2) years), and 144 children who underwent only routine dressing change were enrolled in dressing change alone group (90 males and 54 females, aged 1 (1, 2) years). Fifty-one children without full-thickness burns in eschar removal+dressing change group were enrolled in eschar removal+dressing change group 1 (26 males and 25 females, aged 1 (1, 2) years), and 57 cases of the 83 children with full-thickness burns who did not undergo autologous skin grafting at the same time of early surgery (namely early skin grafting) in eschar removal+dressing change group were included in eschar removal+dressing change group 2 (37 males and 20 females, aged 1 (1, 2) years). Seventy-six children without full-thickness burns in dressing change alone group were included in dressing change alone group 1 (51 males and 25 females, aged 1 (1, 3) years), and 68 children with full-thickness burns in dressing change alone group were included in dressing change alone group 2 (39 males and 29 females, aged 1 (1, 2) years). For deep partial-thickness burn wounds and small full-thickness burn wounds in eschar removal+dressing change group, the eschar removal was performed on the basis of retaining a thin layer of denatured dermis so as to preserve the healthy tissue of the wound base, and ADM was applied to all wounds externally after eschar removal. For larger full-thickness burn wounds in this group, especially those located in the functional part of joints, eschar removal to the plane layer of viable tissue and early autologous skin grafting was needed. When the superficial wounds of children healed or tended to heal, the residual wounds were evaluated, and elective autologous skin grafting was performed if it was difficult to heal within 14 days. The healing time, intervention healing time, times of operation/dressing change, and times of intervention operation/dressing change in children with deep partial-thickness burn wounds of children in eschar removal+dressing change group, dressing change alone group, eschar removal+dressing change group 1, and dressing change alone group 1 were recorded. At the last follow-up (follow-up period was set to 7-12 months), the modified Vancouver scar scale (mVSS) scores of the most severe area of scar hyperplasia of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group and 48 children in dressing change alone group were recorded. The healing time and times of operation/dressing change of all burn wounds of children in eschar removal+dressing change group and dressing change alone group, and the healing time and times of operation/dressing change of full-thickness burn wounds of children in eschar removal+dressing change group 2 and dressing change alone group 2 were recorded. The incidences of wound infection, sepsis, fever, and fever after 5 days of burns in children of eschar removal+dressing change group and dressing change alone group during wound healing. Results: Compared with those in dressing change alone group, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group (with Z values of -11.00, -11.33, -12.64, and -11.65, respectively, P<0.05). Compared with those in dressing change alone group 1, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group 1 (with Z values of 6.57, 6.46, 8.04, and 6.57, respectively, P<0.05). At the last follow-up, the mVSS score of the most severe scar hyperplasia area of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group was 4.00 (3.00,5.00), which was significantly lower than 6.50 (5.00,7.00) of 48 children in dressing change alone group (Z =-4.67, P<0.05).Compared with those in dressing change alone group, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in all burn wounds in eschar removal+dressing change group (with Z values of -5.20 and -6.34, respectively, P<0.05). Compared with those in dressing change alone group 2, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in full-thickness burn wounds in eschar removal+dressing change group 2 (with Z values of -5.22 and -5.73, respectively, P<0.05). During wound healing, the probabilities of fever and fever after 5 days of burns in children of eschar removal+dressing change group were significantly lower than those in dressing change alone group (with χ2 values of 4.13 and 3.91, respectively, P<0.05); only 1 child in dressing change alone group developed sepsis, and there was no statistically significant difference in the wound infection rate of children in the two groups (P>0.05). Conclusions: For children with deep burns, early surgery, and early skin grafting or elective autologous skin grafting as needed, have better short-term and long-term effects than those without early surgery.

[3-O-ß-chacotriosyl glycyrrhetinic acid derivatives as potential small-molecule SARS-CoV-2 fusion inhibitors against SARS-CoV-2 entry into host cells].

OBJECTIVE: To study the inhibitory activities of 3-O-ß-chacotriosyl glycyrrhetinic acid derivatives against the entry of SARS-CoV-2 into host cells. METHODS: With pentacyclic triterpene saponin glycyrrhizic acid (a natural SARS-CoV-2 entry inhibitor) as the lead compound, a series of 3-O-ß-chacotriosyl glycyrrhetinic acid derivatives were designed and synthesized based on hypridization principle, and their inhibitory activities against virus entry were tested in SARS-CoV-2 pseudovirusinfected cells. The antiviral targets of the lead compound 1b was identified by pseudotyped SARS-CoV-2 infection assay and surface plasmon resonance (SPR) assay, and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of 1b on virus-cell membrane fusion. Molecular docking and single amino acid mutagenesis were carried out to analyze the effect of 1b on binding activitiy of S protein. RESULTS: The lead compound 1b showed significant inhibitory effect against Omicron pseudovirus with an EC50 value of 3.28 µmol/L (P < 0.05), and had broad-spectrum antiviral activity against other SARS-CoV-2 pseudovirus. Spike-dependent cell-cell fusion assay demonstrated an inhibitory effect of 1b against SARS-CoV-2 S proteinmediated cell-cell fusion. Molecular docking analysis predicted that the lead compound 1b could be well fitted into a cavity between the attachment (S1) and fusion (S2) subunits at the 3-fold axis, where it formed multiple hydrophobic interactions with Glu309, Ser305, Arg765 and Lys964 residues with a KD value of -8.6 kcal/mol. The compound 1b at 10, 5, 2.5 and 1.25 µmol/L showed a significantly reduced inhibitory activity against the pseudovirus with mutated Arg765, Lys964, Glu309 and Leu303 (P < 0.01). CONCLUSION: 3-O-ß-chacotriosyl glycyrrhetinic acid derivatives are capable of stabilizing spike protein in the pre-fusion step to interfere with the fusion of SARS-CoV-2 with host cell membrane, and can thus serve as potential novel small-molecule SARS-CoV-2 fusion inhibitors.

[Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China].

Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

[Application effects of nitrous oxide and oxygen mixed inhalation technology on analgesia and sedation during debridement and dressing change in children with moderate or severe burns].

Objective: To investigate the application effects of nitrous oxide and oxygen mixed inhalation technology on analgesia and sedation during debridement and dressing change in children with moderate or severe burns. Methods: A retrospective non-randomized contemporary controlled study was conducted. From December 2019 to November 2021, 140 burn children with moderate or severe burns, aged 1 to 3 years, who met the inclusion criteria were admitted to Central Hospital Affiliated to Shandong First Medical University. During debridement and dressing change 3 to 14 days after injury, 42 children, including 23 males and 19 females, who received nurse-centered pain management mode and analgesia and sedation with nitrous oxide and oxygen mixed inhalation technology were included in nitrous oxide group (the dressing change process using the above-mentioned technology for the first time was selected for the follow-up study). Another 42 children, including 24 males and 18 females, were included in non-nitrous oxide group from 98 children who did not apply analgesia or sedation treatment during dressing change with stratified random sampling (one dressing change process was randomly selected for the follow-up study). The face, legs, activity, cry, and consolability scale and Ramsay sedation scale were used to evaluate the pain intensity and degree of sedation, respectively, at 30 minutes before dressing change (hereinafter referred to as before dressing change), immediately after debridement, and at 30 minutes after finishing dressing change (hereinafter referred to as after dressing change). After dressing change, the self-made satisfaction scale was used to evaluate the satisfaction degree of dressing change surgeons and guardians of children for analgesic effects during dressing change. The duration of dressing change and the healing time of deep partial-thickness burn wounds were recorded. The heart rate and percutaneous arterial oxygen saturation (SpO2) before, during, and after dressing change and the occurrence of adverse events such as nausea and vomiting during dressing change were recorded. Data were statistically analyzed with Mann-Whitney U test, chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. Results: There were no significant differences in the score of pain intensity and score of sedation degree between children in two groups before and after dressing change (P>0.05). Immediately after debridement, the score of pain intensity of children in nitrous oxide group was 2.5±0.7, which was significantly lower than 7.6±1.0 in non-nitrous oxide group (t=-26.69, P<0.05); the score of sedation degree of children in nitrous oxide group was 1.83±0.38, which was significantly higher than 1.21±0.42 in non-nitrous oxide group (t=7.15, P<0.05). After dressing change, the satisfaction degree scores of dressing change surgeons and guardians of children for analgesic effects during dressing change of children in nitrous oxide group were significantly higher than those in non-nitrous oxide group (with t values of 10.53 and 2.24, respectively, P<0.05). The dressing change duration of children in nitrous oxide group was significantly shorter than that in non-nitrous oxide group (t=-5.33, P<0.05). The healing time of deep partial-thickness burn wounds in children between the two groups had no significant difference (P>0.05). The heart rate of children in nitrous oxide group was significantly lower than that in non-nitrous oxide group during dressing change (t=-12.40, P<0.05), while the SpO2 was significantly higher than that in non-nitrous oxide group (t=5.98, P<0.05). During dressing change, 2 children had nausea and 1 child had euphoria in nitrous oxide group, while heart rate of all children in non-nitrous oxide group continued to be higher than the normal range. Conclusions: In the process of debridement and dressing change in children with moderate or severe burns, the use of nurse-centered pain management mode and the standardized use of nitrous oxide and oxygen mixed inhalation technology can safely and effectively control pain and sedation.

[Malignant peripheral nerve sheath tumor: a clinicopathological analysis].

Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.

[Safety and efficacy of transcatheter aortic valve replacement using the "All in One" single artery/vessel technique].

Objective: To explore the safety and efficacy of transcatheter aortic valve replacement (TAVR) using the "All in One" single-artery/vessel technique. Methods: This is a retrospective study. A total of 30 consecutive patients underwent TAVR using the single artery/vascular technique in Beijing Anzhen Hospital from August to December 2021 were included. Baseline clinical data, operative situation, postoperative outcomes, and incidence of adverse events during hospitalization and at one month post TAVR were analyzed. Results: Mean age was (72.6±9.7) years, 16 were male patients, STS score was (4.73±3.12)%. Four patients were diagnosed as isolated aortic regurgitation (all with tricuspid aortic valves), and 26 patients were diagnosed as aortic stenosis (AS), 10 of whom with tricuspid aortic valves and 16 of whom with bicuspid aortic valves. The single-vessel technique was applied in 3 aortic stenosis cases; the single-artery technique was applied in 27 cases. Echocardiography was performed immediately after procedure and results showed no or trace perivalvular leak in 27 cases and small perivalvular leak in 3 cases; the mean aortic transvalvular gradient of 26 AS patients decreased from (50.4±16.0) mmHg (1 mmHg=0.133 kPa) to (9.4±3.2) mmHg (P<0.001). The procedure time was (64.8±18.9) min. There were no intraoperative death, valve displacement, conversion to surgery, coronary artery occlusion in all 30 patients. There were no major cardiac adverse events such as myocardial infarction or stroke occurred during hospitalization or at follow-up. One-month follow-up echocardiography indicated prosthesis works well. The symptoms were significantly alleviated, and the Kansas City Cardiomyopathy Score (KCCQ score) of all patients increased from 48.1±18.4 to 73.5±17.6 (P<0.001). Conclusions: TAVR using the single artery/vessel technique is safe and feasible. This technique is related to reduced access complications and worthy of wide application.

[Feasibility study of using bridging temporary permanent pacemaker in patients with high-degree atrioventricular block after TAVR].

Objective: To determine the feasibility of using temporary permanent pacemaker (TPPM) in patients with high-degree atrioventricular block (AVB) after transcatheter aortic valve replacement (TAVR) as bridging strategy to reduce avoidable permanent pacemaker implantation. Methods: This is a prospective observational study. Consecutive patients undergoing TAVR at Beijing Anzhen Hospital and the First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were screened. Patients with high-degree AVB and TPPM were included. Patients were followed up for 4 weeks with pacemaker interrogation at every week. The endpoint was the success rate of TPPM removal and free from permanent pacemaker at 1 month after TPPM. The criteria of removing TPPM was no indication of permanent pacing and no pacing signal in 12 lead electrocardiogram (EGG) and 24 hours dynamic EGG, meanwhile the last pacemaker interrogation indicated that ventricular pacing rate was 0. Routinely follow-up ECG was extended to 6 months after removal of TPPM. Results: Ten patients met the inclusion criteria for TPPM, aged (77.0±11.1) years, wirh 7 females. There were 7 patients with third-degree AVB, 1 patient with second-degree AVB, 2 patients with first degree AVB with PR interval>240 ms and LBBB with QRS duration>150 ms. TPPM were applied on the 10 patients for (35±7) days. Among 8 patients with high-degree AVB, 3 recovered to sinus rhythm, and 3 recovered to sinus rhythm with bundle branch block. The other 2 patients with persistent third-degree AVB received permanent pacemaker implantation. For the 2 patients with first-degree AVB and LBBB, PR interval shortened to within 200 ms. TPPM was successfully removed in 8 patients (8/10) at 1 month without permanent pacemaker implantation, of which 2 patients recovered within 24 hours after TAVR and 6 patients recovered 24 hours later after TAVR. No aggravation of conduction block or permanent pacemaker indication were observed in 8 patients during follow-up at 6 months. No procedure-related adverse events occurred in all patients. Conclusion: TPPM is reliable and safe to provide certain buffer time to distinguish whether a permanent pacemaker is necessary in patients with high-degree conduction block after TAVR.

[Network meta-analysis comparing the clinical outcomes and safety of robotic, laparoscopic, and transanal total rectal mesenteric resection for rectal cancer].

Objective: To methodically assess the clinical effectiveness and safety of robot-assisted total rectal mesenteric resection (RTME), laparoscopic-assisted total rectal mesenteric resection (laTME), and transanal total rectal mesenteric resection (taTME). Methods: A computer search was conducted on PubMed, Embase, Cochrane Library, and Ovid databases to identify English-language reports published between January 2017 and January 2022 that compared the clinical efficacy of the three surgical procedures of RTME, laTME, and taTME. The quality of the studies was evaluated using the NOS and JADAD scales for retrospective cohort studies and randomized controlled trials, respectively. Direct meta-analysis and reticulated meta-analysis were performed using Review Manager software and R software, respectively. Results: Twenty-nine publications comprising 8,339 patients with rectal cancer were ultimately included. The direct meta-analysis indicated that the length of hospital stay was longer after RTME than after taTME, whereas according to the reticulated meta-analysis the length of hospital stay was shorter after taTME than after laTME (MD=-0.86, 95%CI: -1.70 to -0.096, P=0.036). Moreover, the incidence of anastomotic leak was lower after taTME than after RTME (OR=0.60, 95%CI: 0.39 to 0.91, P=0.018). The incidence of intestinal obstruction was also lower after taTME than after RTME (OR=0.55, 95%CI: 0.31 to 0.94, P=0.037). All of these differences were statistically significant (all P<0.05). There were no statistically significant differences between the three surgical procedures regarding the number of lymph nodes cleared, length of the inferior rectal margin, or rate of positive circumferential margins (all P>0.05). An inconsistency test using nodal analysis revealed no statistically significant differences between the results of direct and indirect comparisons of the six outcome indicators (all P>0.05). Furthermore, we detected no significant overall inconsistency between direct and indirect evidence. Conclusion: taTME has advantages over RTME and laTME, in terms of radical and surgical short-term outcomes in patients with rectal cancer.

A Novel MR Imaging Sequence of 3D-ZOOMit Real Inversion-Recovery Imaging Improves Endolymphatic Hydrops Detection in Patients with Ménière Disease.

BACKGROUND AND PURPOSE: The detection rate of premortem MR imaging endolymphatic hydrops is lower than that of postmortem endolymphatic hydrops in Ménière disease, indicating that current MR imaging techniques may underestimate endolymphatic hydrops. Therefore, we prospectively investigated whether a novel high-resolution MR imaging technique, the 3D zoomed imaging technique with parallel transmission real inversion-recovery (3D-ZOOMit real IR), would improve the detection of endolymphatic hydrops compared with conventional 3D TSE inversion-recovery with real reconstruction. MATERIALS AND METHODS: Fifty patients with definite unilateral Ménière disease were enrolled and underwent 3D-ZOOMit real IR and 3D TSE inversion-recovery with real reconstruction 6 hours after IV gadolinium injection. The endo- and perilymph spaces were scored separately. The contrast-to-noise ratio, SNR, and signal intensity ratio of the 2 sequences were respectively calculated and compared. The presence of endolymphatic hydrops was evaluated. RESULTS: The endolymphatic space in the cochlea and vestibule was better visualized with 3D-ZOOMit real IR than with conventional 3D TSE inversion-recovery with real reconstruction (P < .001). There were differences between the 2 sequences in the evaluation of no cochlear hydrops and cochlear hydrops (both, P < .017). All contrast-to-noise ratio, SNR, and signal intensity ratio values of 3D-ZOOMit real IR images were statistically higher than those of conventional 3D TSE inversion-recovery with real reconstruction (all, P < .001). CONCLUSIONS: The 3D-ZOOMit real IR sequences are superior to conventional 3D TSE inversion-recovery with real reconstruction sequences in visualizing the endolymphatic space, detecting endolymphatic hydrops, and discovering contrast permeability.

[Effect of nanofat combined with platelet-rich plasma for treatment of pressure injury wounds in rats].

OBJECTIVE: To investigate the effect of allogeneic nanofat combined with platelet-rich plasma (PRP) for treatment of pressure injury wounds in rats. METHODS: Forty SD rat models with pressure injury wounds were randomly divided into 4 groups (n=10) for treatment with nanofat, PRP (platelet count about 6.2 times that of normal whole blood), nanofat combined with PRP, or PBS only (control group).Wound healing was observed on days 1, 3, 5, 7, 10 and 14 and wound healing rate was calculated. On days 5, 10 and 14, tissue samples were taken from the wounds for HE staining, Masson staining, immunohistochemistry, and Western blotting to observe inflammatory cell infiltration, collagen formation, deposition and arrangement, angiogenesis, inflammatory factor expression and VEGF expression in the wounds. RESULTS: The combined treatment with nanofat and PRP achieved the highest wound healing rates at all the time points of observation (P < 0.05), enhanced inflammatory cell infiltration on day 5, and accelerated dermal and epidermal growth compared with the other treatments (P < 0.05). The combined treatment also more effectively promoted collagen expression and its regular arrangement (P < 0.05) and enhanced angiogenesis in the wounds than nanofat and PRP alone, without significant difference between the latter two treatments (P > 0.05). Immunohistochemistry and Western blotting showed that the expressions of MCP-1 and VEGF in the wounds were the highest in the combined treatment group (P < 0.05) and were higher in nanofat and PRP treatment groups than in the control group (P < 0.05). CONCLUSION: Nanofat combined with PRP can significantly promote healing of pressure injury wounds in rats, and their synergistic effect sheds light on a new strategy for treatment of pressure injury wounds.

BACH1 regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells.

BACKGROUND: The preservation of biological and physiological vitality as well as the formation of dentin are among the main tasks of human dental pulp for a life time. Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) exhibits the capacity of dental pulp regeneration and dentin complex rebuilding. Exploration of the mechanisms regulating differentiation and proliferation of hDPSCs may help to investigate potential clinical applications. BTB and CNC homology 1 (BACH1) is a transcription repressor engaged in the regulation of multiple cellular functions. This study aimed to investigate the effects of BACH1 on the proliferation and odontoblastic differentiation of hDPSCs in vitro. METHODS: hDPSCs and pulpal tissues were obtained from extracted human premolars or third molars. The distribution of BACH1 was detected by immunohistochemistry. The mRNA and protein expression of BACH1 were examined by qRT-PCR and Western blot analysis. BACH1 expression was regulated by stable lentivirus-mediated transfection. Cell proliferation and cell cycle were assessed by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay and flow cytometry. The expression of mineralization markers, alkaline phosphatase (ALP) activity and alizarin red S staining were conducted to assess the odontoblastic differentiation ability. RESULTS: BACH1 expression was stronger in the odontoblast layer than in the cell rich zone. The total and nuclear protein level of BACH1 during odontoblastic differentiation was downregulated initially and then upregulated gradually. Knockdown of BACH1 greatly inhibited cell proliferation, arrested cell cycle, upregulated the heme oxygenase-1 (HO-1) expression and attenuated ALP activity, decreased calcium deposits and downregulated the expression of mineralization markers. Treatment of Tin-protoporphyrin IX, an HO-1 inhibitor, failed to rescue the impaired odonto/osteogenic differentiation capacity. Overexpression of BACH1 increased cell proliferation, ALP activity and the expression of mineralization markers. CONCLUSIONS: Our findings suggest that BACH1 is an important regulator of the proliferation and odontoblastic differentiation of hDPSCs in vitro. Manipulation of BACH1 expression may provide an opportunity to promote the regenerative capacity of hDPSCs.

[CIC-rearranged sarcoma with rhabdoid features: a clinicopathological analysis].

Objective: To investigate the histopathologic, immunohistochemical, molecular genetic characteristics of CIC-rearranged sarcoma (CRS) with rhabdoid features. Methods: The clinical and pathologic data of two cases of CRS diagnosed between 2019 and 2021 at the Department of Pathology, Jiangsu Province Hospital were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The relevant literature was reviewed. Results: Both patients were female, one was 58 years old, with tumor located in left thigh; the other was 43 years old, with tumor located in left pelvic cavity. Microscopically, both tumors were composed of small to medium-sized round, oval cells, arranged in nodules or sheets. The tumor cells showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Both cases showed rhabdoid phenotype with myxoid stromal changes. Immunohistochemically, both cases were positive for CD99 and c-myc. High WT1 reactivity was seen in classic area, with low reactivity in rhabdoid area. There was no INI1 lost in both cases. Both were negative for NKX2.2 and NKX3.1. By FISH both cases demonstrated convincing break-apart signals of CIC gene. One patient died of disease after 1 month, and the other died of disease after 3 months. Conclusions: CRS is a small round cell undifferentiated sarcoma of the bone and soft tissue defined by molecular genetic characteristics, and may show atypical morphologic and immunophenotypic characteristics such as rhabdoid features. A correct understanding of its rare morphologic and immunophenotypic characteristics, combined with molecular pathologic detection, is conducive to correct diagnosis.

[Chronic active Epstein-Barr virus infection in the gastrointestinal tract: a clinicopathological study of three cases].

Objective: To study the clinicopathological features of chronic active Epstein-Barr virus infection (CAEBV) in the digestive tract and to discuss its differential diagnosis. Methods: The clinical data of 3 cases of CAEBV in the digestive tract diagnosed in Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), Nanjing, China from December 2018 to August 2020 were collected. Three cases of CAEBV were evaluated using histology, immunohistochemistry and in situ hybridization. The related literature was reviewed. Results: Three patients were all males, aged 33, 32 and 31 years, respectively. All patients had a history of intermittent fever and repeated diarrhea for the past years with persistent increase in EB viral load (DNA copies) in peripheral blood. Endoscopically, intestinal tract was involved in all cases with ulcers, and esophagus was involved concurrently in 1 case showing nodular lesions. Microscopically, there were moderate polymorphic inflammatory infiltrate with lymphoid component displaying no or mild atypia in all cases and deep fissuring ulcers in one case (case 3). All tumor cells were positive for CD3 and TIA-1, and negative for CD56 and CD5. Cases 1 and 2 showed CD4-/CD8-, whereas case 3 displayed CD4+/CD8-. In situ hybridization for Epstein-Barr virus-encoded RNA was positive in all 3 cases. Follow-up data showed that cases 1 and 2 were free of disease progression at the end of follow-up (16 months and 17 months, respectively). However, case 3 progressed to extranodal NK/T-cell lymphoma 22 months after the initial diagnosis. Conclusions: CAEBV of the digestive tract is a rare lymphoid proliferative disorder with potential transformation to extranodal NK/T-cell lymphoma. It is a great mimicker of inflammatory bowel disease, especially in small biopsy specimens. It is important to integrate clinicopathological, radiological and laboratory data to avoid misdiagnosis.

[Correlation of VISTA and PD-L1 expression with the clinicopathological features and prognosis in triple-negative breast cancer].

Objective: To investigate the expression of VISTA and PD-L1 in triple-negative breast cancer (TNBC) and to explore its relationship with clinicopathologic features and prognosis. Methods: Ninety TNBC patients who underwent surgical resections between 2016 to 2018 in Jiangsu Province Hospital were selected. The expression of VISTA and PD-L1 in both tumor cells and immune cells was evaluated by immunohistochemistry, and the relationship with clinicopathologic parameters and prognosis was analyzed. Results: VISTA was expressed in 17.8% (16/90) of the tumors. The expression of VISTA in tumor cells was related to a higher Ki-67 proliferation index (P=0.02) and higher number of tumor-infiltrating lymphocytes (TIL, P<0.01). VISTA was expressed in 71.1% (64/90) of the immune cells and the expression correlated with smaller tumor size (P=0.02), lower T stage (P=0.04), higher number of TIL (P<0.01), higher number of CD8+T cells (P=0.03) and higher Ki-67 proliferation index (P=0.02). PD-L1 was expressed in 17.8% (16/90) of the immune cells and the expression correlated with higher histologic grade (P=0.04), higher Ki-67 proliferation index (P=0.02) and higher number of TIL (P<0.01). VISTA expression was higher in immune cells within TNBC patients than PD-L1 (P<0.01). Among 90 TNBC patients, complete follow-up was obtained in 85 patients, 8 of whom had recurrences or metastasis after surgery, and two patients cases died of recurrences or metastasis. Conclusions: The expression rate of VISTA is higher than that of PD-L1 in TNBC. The expression of VISTA in immune cells predicts a lower T stage. VISTA may act as an effective immunotherapy target.

[Effect of rotigotine on the quality of emergence from general anesthesia in patients undergoing deep brain stimulation].

Objective: To investigate the effect of rotigotine on the quality of emergence from general anesthesia in patients undergoing deep brain stimulation (DBS). Methods: A total of 42 patients (31 males and 11 females, aged 55-85 years) undergoing DBS surgery under general anesthesia in the First Affiliated Hospital of Zhengzhou University from March 2020 to October 2021 were selected. The patients were divided into non-rotigotine group (n=21) and rotigotine group (n=21) by using a random number table according to whether rotigotine patch was used. Postoperative recovery time, extubation time, length of postanesthesia care unit (PACU) stay, and grades of muscle tension, swallowing function and salivary secretion during recovery were compared between the two groups. Meanwhile, the incidence of adverse events during extubation was also compared. Results: The postoperative recovery time, extubation time and length of PACU stay in rotigotine group were (20.3±2.6) min, (30.6±3.1) min and (46.4±3.9) min, respectively, which were shorter than those of non-rotigotine group [(29.0±5.8) min, (42.6±10.0) min and (63.0±18.9) min, respectively] (all P<0.05). The grades of postoperative muscle tension, swallowing function and salivary secretion in rotigotine group [M(Q1, Q3)] were 1(1, 2), 1(1, 2) and 1(1, 1), respectively, which were lower than those of non-rotigotine group [2(2, 3), 2(2, 2) and 2(1, 2), respectively] (P=0.001, 0.002 and 0.011). The incidence of adverse events during anesthesia extubation in rotigotine group was 14.3% (3/21), which was lower than that of non-rotigotine group [42.9% (9/21), P=0.040]. Conclusion: Rotigotin patch is helpful to improve the quality of emergence from general anesthesia in patients undergoing DBS and reduce the occurrence of adverse events during extubation.