[Clinical analysis of 18 children with aggressive mature B-cell lymphoma after liver transplantation].

Objective: To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation. Methods: This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis. Results: Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions: The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

[Intraoperative optical coherence tomography guided precise corneal suture in the treatment of acute keratoconus].

Objective: This study aimed to observe the clinical efficacy of precise suturing of posterior elastic layer fissures guided by intraoperative optical coherence tomography (OCT) in conjunction with anterior chamber puncture and drainage, and corneal thermokeratoplasty for the treatment of severe acute edematous keratoconus. Methods: Non-randomized controlled trial. Data were collected for a study involving 31 cases of acute edematous keratoconus patients who underwent surgical treatment at the Shandong Eye Hospital between June 2017 and July 2021. Among them, there were 30 male and 1 female patients, with an age range of 11 to 32 years and a mean age of (19.80±5.80) years. Eighteen patients in the study group underwent precise suturing of posterior elastic layer fissures guided by intraoperative OCT, in combination with anterior chamber puncture and drainage, and corneal thermokeratoplasty. Thirteen patients in the control group did not undergo suturing. Preoperative visual acuity, corneal edema diameter, corneal thickness, and posterior elastic layer fissure length were collected. Evaluation was performed using slit lamp microscopy, anterior segment OCT, and other methods to assess the time of initial postoperative corneal edema resolution and closure of the posterior elastic layer fissure. Deep lamellar keratoplasty was performed 2 to 4 weeks after edema resolution, and the corneal bed scar repair and visual acuity of the two groups were compared. Results: In the suturing group, the corneas of all 18 patients were accurately sutured to the deep stromal layer near the posterior elastic layer. The time for corneal edema resolution was 2.50 (1.00, 6.25) days in the suturing group and 7.00 (6.00, 10.50) days in the control group. The fissure healing time was 7.50 (7.00, 12.00) days in the suturing group and 14.00 (9.00, 14.00) days in the control group. The differences were statistically significant (all P<0.05). After 2 weeks, the central corneal thickness decreased to (529.80±174.50) µm in the suturing group and (612.00±205.12) µm in the control group. The suturing group showed accurate corneal suturing to the deep stromal layer near the posterior elastic layer, resulting in central corneal flattening, closure of voids in the stroma, and a significant decrease in corneal thickness. All 18 patients in the suturing group successfully completed deep lamellar keratoplasty, with 6 cases (6/18) experiencing mild graft bed leakage during surgery but without affecting the deep lamellar keratoplasty. One year postoperatively, the visual acuity (logarithm of the minimum resolution angle) was 0.23±0.12 in the suturing group and 0.33±0.11 in the control group, with a statistically significant difference (P<0.05). Conclusions: In the treatment of severe acute edematous keratoconus, precise suturing of posterior elastic layer fissures guided by intraoperative OCT, in conjunction with anterior chamber puncture and drainage, and corneal thermokeratoplasty, can rapidly alleviate corneal edema and promote the healing of posterior elastic layer fissures. This approach achieves better visual outcomes for subsequent lamellar keratoplasty surgeries. The use of intraoperative OCT guidance allows accurate positioning of the posterior elastic layer fissure in terms of location, direction, and depth of corneal stromal voids, thereby assisting surgeons in precise suturing.

[Application of intraoperative optical coherence tomography in deep lamellar keratoplasty].

Objective: To evaluate the clinical application value of intraoperative optical coherence tomography (iOCT) in deep anterior lamellar keratoplasty (DALK) using the big-bubble technique to bare Descemet's membrane. Methods: Retrospective case series. Clinical data of 92 patients (92 eyes) with monocular stromal corneal diseases who underwent big-bubble DALK in the Eye Hospital of Shandong First Medical University from January 2020 to August 2021 were collected. There were 53 males and 39 females. The average age was (53.2±16.0) years old. All patients underwent iOCT scanning to determine the location and depth of the injection needle after initial removal of the corneal lesion, to observe the integrity of the recipient bed, Descemet's membrane, after complete lesion removal, and to observe the adhesion between the corneal graft and the recipient bed and check folds on the recipient bed after suturing of the corneal graft. The intraoperative perforation of Descemet's membrane, postoperative thickness of the cornea and the recipient bed, visual acuity, and corneal astigmatism were recorded. Results: By iOCT, the thickness of the recipient bed was found to be about 1/2 of the corneal thickness and relatively uniform in all directions in 62 eyes (67.4%), so the sterile air was injected from the center of the recipient bed to separate it from the stromal layer. In 30 eyes (32.6%) with an uneven thickness of the recipient bed, the sterile air was injected from the paracentral area of the recipient bed. Under the guidance of iOCT scanning, 89 eyes (96.7%) did not experience any perforation of Descemet's membrane during surgery. The Descemet's membrane folds in the central 5-mm area of the recipient bed was observed and flattened in 20 eyes with the assistance of iOCT scanning. The postoperative corneal thickness was (578.95±108.26) µm, and the recipient bed thickness was (36.06±23.11) µm. The best corrected visual acuity of all patients at 6 months after surgery was 0.57±0.25 logMAR, which was significantly better than that before surgery (1.61±1.27 logMAR; P<0.001). The average corneal astigmatism at 6 months after surgery was (2.72±2.44) diopters. Conclusions: The application of iOCT scanning in DALK surgery assisted by the big-bubble method can provide safe guidance for surgeons to adopt correct surgical procedures, decrease the risk of Descemet's membrane perforation, reduce the recipient bed folds, and facilitate corneal interlayer adhesion, thereby improving the visual prognosis.

Non-cell-autonomous cancer progression from chromosomal instability.

Chromosomal instability (CIN) is a driver of cancer metastasis1-4, yet the extent to which this effect depends on the immune system remains unknown. Using ContactTracing-a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell-cell interactions from single-cell transcriptomic data-we show that CIN-induced chronic activation of the cGAS-STING pathway promotes downstream signal re-wiring in cancer cells, leading to a pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING and a corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal of CIN, depletion of cancer cell STING or inhibition of ER stress response signalling abrogates CIN-dependent effects on the tumour microenvironment and suppresses metastasis in immune competent, but not severely immune compromised, settings. Treatment with STING inhibitors reduces CIN-driven metastasis in melanoma, breast and colorectal cancers in a manner dependent on tumour cell-intrinsic STING. Finally, we show that CIN and pervasive cGAS activation in micronuclei are associated with ER stress signalling, immune suppression and metastasis in human triple-negative breast cancer, highlighting a viable strategy to identify and therapeutically intervene in tumours spurred by CIN-induced inflammation.

Breast lymphoma: General review.

BACKGROUND: Lymphoma of the breast can be classified as either primary breast lymphoma (PBL) or secondary to systemic lymphoma (SBL). PBL is a rare disease with Diffuse Large B cell Lymphomas (DLBCL) being the most common subtype. OBJECTIVES: In the current study, we represented eleven cases diagnosed with breast lymphoma in our trust; two of them had PBL and nine had SBL. We focused mainly on the clinical presentation, diagnosis, management and outcomes. METHODS: We did this retrospective review for all breast lymphoma patients who were diagnosed in our trust during the periods from 2011-2022. Patients' data were obtained from the hospital recording system. We followed up these patients thus far to identify the outcome of treatment in each patient. RESULTS: Eleven patients were included in our review. All patients were females. Average age of diagnosis was 66.1 ± 13 years of age. Eight patients were diagnosed with DLBCL, two patients were diagnosed with follicular lymphomas, and the last one had lymphoplasmacytic lymphoma. Chemotherapy +∕- radiotherapy was the standard treatment regimen in all patients. Four patients passed away within one year of chemotherapy, five patients achieved complete remission, one patient had two relapses and is still under treatment, while the last patient was diagnosed recently and still awaiting treatment. CONCLUSION: Primary breast lymphoma is an aggressive disease. The treatment for PBL is mainly systemic with chemoradiotherapy. The role of surgery is now limited to the diagnosis of the disease. Early diagnosis and proper treatment are crucial for the management of such cases.

Innovations in the Treatment of Dystrophic Epidermolysis Bullosa (DEB): Current Landscape and Prospects.

Dystrophic epidermolysis bullosa (DEB) is one of the major types of EB, a rare hereditary group of trauma-induced blistering skin disorders. DEB is caused by inherited pathogenic variants in the COL7A1 gene, which encodes type VII collagen, the major component of anchoring fibrils which maintain adhesion between the outer epidermis and underlying dermis. DEB can be subclassified into dominant (DDEB) and recessive (RDEB) forms. Generally, DDEB has a milder phenotype, while RDEB patients often have more extensive blistering, chronic inflammation, skin fibrosis, and a propensity for squamous cell carcinoma development, collectively impacting on daily activities and life expectancy. At present, best practice treatments are mostly supportive, and thus there is a considerable burden of disease with unmet therapeutic need. Over the last 20 years, considerable translational research efforts have focused on either trying to cure DEB by direct correction of the COL7A1 gene pathology, or by modifying secondary inflammation to lessen phenotypic severity and improve patient symptoms such as poor wound healing, itch, and pain. In this review, we provide an overview and update on various therapeutic innovations for DEB, including gene therapy, cell-based therapy, protein therapy, and disease-modifying and symptomatic control agents. We outline the progress and challenges for each treatment modality and identify likely prospects for future clinical impact.

[Characteristics of serum autoantibodies in patients with lupus nephritis and tubulointerstitial damage].

OBJECTIVE: To observe the tubulointerstitial damage (TID) in lupus nephritis (LN) and investigate the relationship between autoantibodies and TID in lupus nephritis. METHODS: This cross-sectional study was conducted in a comprehensive tertiary hospital in Peking University Shenzhen Hospital. From March 2012 to July 2021, LN patients who performed renal biopsy were enrolled in the study. Clinical, laboratory and pathology data were collected. We classified the patients into none-or-mild group and moderate-to-severe groups according to the severity of interstitial fibrosis (IF) /tubular atrophy (TA) or tubulointerstitial inflammation (TII). The t test, U test and Chi-square test were used for statistical analysis as appropriate. RESULTS: A total of 226 patients were included, of who 190 (84%) were female with a median age of 32 (26, 39) years. 89% (201/226) of the patients who pathologically proved to be proliferative LN by renal biopsy. The frequency of moderate-to-severe TII and moderate-to-severe IF/TA was 30% (67/226) and 34% (76/226) respectively. For autoantibodies, the patients with moderate-to-severe TII had a lower rate of positive serum anti-ribonucleoprotein (anti-RNP) antibodies than the patients with none-or-mild TII (34% vs. 51%), and moderate-to-severe IF/TA had a lower rate of positive anti-ribosomal P protein (anti-P) antibodies than patients with none-or-mild IF/TA (19% vs. 33%). For other clinical indicators, the patients with moderate-to-severe TII and moderate-to-severe IF/TA were more often combined with proliferative LN, hypertension and anemia than the patients with none-or-mild TII and none-or-mild IF/TA, respectively. The patients with moderate-to-severe TII had higher serum creatinine values and lower glomerular filtration rates than the patients with none-or-mild TII. The patients with moderate-to-severe IF/TA had higher serum creatinine values, and lower glomerular filtration rates than the patients with none-or-mild IF/TA. CONCLUSION: In patients with LN in Southern China, anti-RNP antibodies and anti-P antibodies may be potential protective factors for TII and IF/TA, respectively. More studies are needed to identify the risk factors of lupus patients with TID and investigate the correlation between autoantibodies and TID, which are critical for developing better preventive and therapeutic strategies to improve the survival rate of LN.

Docosahexaenoic Acid Reverses Epithelial-Mesenchymal Transition and Drug Resistance by Impairing the PI3K/AKT/ Nrf2/GPX4 Signalling Pathway in Docetaxel-Resistant PC3 Prostate Cancer Cells.

Drug resistance is a serious problem in cancer therapy. Growing evidence has shown that docosahexaenoic acid has anti-inflammatory and chemopreventive abilities. Studies have shown that autophagy inhibition and ferroptosis are promising therapeutic strategies for overcoming multidrug resistance. This study was aimed to examine whether docosahexaenoic acid (DHA) could reverse docetaxel resistance in prostate cancer cells. Cell survival was examined by MTT and colony formation. Protein expression was determined by Western blot. Reactive oxygen species (ROS) production was measured by flow cytometry. DHA displayed anti-cancer effects on proliferation, colony formation, migration, apoptosis, autophagy and epithelial mesenchymal transition. Glutathione-S-transferase π is an enzyme that plays an important role in drug resistance. DHA inhibited GSTπ protein expression and induced cytoprotective autophagy by regulating the PI3K/AKT signalling pathway in PC3R cells. DHA combined with PI3K inhibitor (LY294002) enhanced apoptosis by alleviating the expression of LC3B, (pro-) caspase- 3 and (uncleaved) PARP. DHA induced ferroptosis by attenuating the expression of glutathione peroxidase 4 (GPX4) and nuclear erythroid 2-related factor 2 (Nrf2). DHA-treated PC3R cells produced ROS. The ROS and cytotoxicity were reversed by treatment with ferrostatin-1. DHA combined with docetaxel inhibited EMT by regulating the expression of E-cadhein and N-cadherin. In summary, DHA reversed drug resistance and induced cytoprotective autophagy and ferroptosis by regulating the PI3K/AKT/Nrf2/GPX4 signalling pathway in PC3R cells. We propose that DHA could be developed as a chemosensitizer and that the PI3K/AKT /Nrf2/GPX4 signalling pathway might be a promising therapeutic target for overcoming cancer drug resistance.

[Analysis of 42 cases of childhood superior vena cava syndrome associated with mediastinal malignancy].

Objective: To summarize the clinical features, management and outcome of superior vena cava syndrome (SVCS) associated with mediastinal malignancy in children. Methods: Clinical data of 42 children of SVSC associated with mediastinal malignancy in Shanghai Children's Medical Center from January 2015 to December 2021 were collected and analyzed retrospectively. The clinical manifestations, pathological diagnosis, disease diagnosis process, and prognosis were summarized. Results: Among 42 children of SVCS associated with mediastinal malignancy, there were 31 males and 11 females. The age at diagnosis was 8.5 (1.9, 14.9) years. Cough and wheezing (33 cases, 79%), orthopnea (19 cases, 45%) and facial edema (18 cases, 43%) occurred most commonly. T-cell lymphoblastic lymphoma (T-LBL) was the most frequent pathological diagnosis (25 cases, 60%), followed by T-cell acute lymphoblastic leukemia (T-ALL) (7 cases, 17%), anaplastic large cell lymphoma (4 cases, 10%) and diffuse large B-cell lymphoma (2 cases, 5%), peripheral T-lymphoma, Hodgkin lymphoma, Ewing's sarcoma and germ cell tumor (1 case each). Pathological diagnosis was confirmed by bone marrow aspiration or thoracentesis in 14 cases, peripheral lymph node biopsy in 6 cases, and mediastinal biopsy in 22 cases. Twenty-seven cases (64%) had local anesthesia. Respiratory complications due to mediastinal mass developed in 3 of 15 cases who received general anesthesia. Of the 42 cases, 27 cases had sustained remission, 1 case survived with second-line therapy after recurrence, and 14 cases died (2 cases died of perioperative complications and 12 cases died of recurrence or progression of primary disease). The follow-up time was 36.7 (1.2, 76.1) months for 27 cases in continuous complete remission. The 3-year overall survival (OS) and events free survival (EFS) rates of 42 children were 59% (95%CI 44%-79%) and 58% (95%CI 44%-77%) respectively. Conclusions: SVCS associated with mediastinal malignancy in children is a life-threatening tumor emergency with high mortality. The most common primary disease is T-LBL. The most common clinical symptoms and signs are cough, wheezing, orthopnea and facial edema. Clinical management should be based on the premise of stable critical condition and confirm the pathological diagnosis through minimal invasive operation.

Effects of regional anaesthesia on mortality in patients undergoing lower extremity amputation: A retrospective pooled analysis.

Background and Aims: Lower extremity amputation (LEA) is a commonly performed surgery and is associated with significant mortality and morbidity. This review compares the impact of anaesthetic technique on 30-day mortality and other perioperative outcomes in patients undergoing LEA. Methods: A systematic search of databases including PubMed, Embase, Scopus and Cochrane Central Register of Controlled Trials, from January 2010 to March 2021, was performed. Studies were eligible if they compared 30-day mortality following either general anaesthesia (GA) or regional anaesthesia (RA), in adult patients undergoing LEA. Results: Ten retrospective observational studies were identified. Four of these studies utilised a propensity-score matching technique. Based on these four studies, RA when compared to GA, is not associated with a reduction in the 30-day mortality (Odds ratio 0.83, 95% confidence interval (CI): 0.65, 1.05, I2 20%, P = 0.12). Also there is a very low level of evidence that RA may result in a decrease in the hospital length-of-stay and intensive care unit admissions of patients undergoing LEA. Conclusion: RA does not decrease the 30-day postoperative mortality in patients undergoing LEA when compared to GA.

[Analysis of long-term efficacy and influencing factors of subthalamic nuclear stimulation for isolated dystonia].

Objective: To evaluate the long-term efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) in the treatment of isolated dystonia, and explore the factors influencing the results. Methods: The clinical data of 23 consecutive patients with isolated dystonia treated with STN-DBS in the Department of Neurosurgery, Tangdu Hospital, Air Force Military Medical University from December 2004 to December 2014,were retrospectively analyzed. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to quantify the dystonia symptoms and signs. Multiple linear regression analysis was used to explore the influencing factors of the results. Results: The age of the 23 patients including 8 females and 15 males was 19(10, 27) years old. The follow-up time was 5-12 years, with an average of (8.1±1.8) years.Compared with the preoperative period, the BFMDRS movement score decreased by 30.1 [95% confidence interval (CI): 12.3-47.8)] points, 34.7 (95%CI: 17.0-52.4) points, 34.1 (95%CI: 16.4-51.8) points and 34.0 (95%CI: 16.3-51.7) points (all P<0.001) respectively at 1 year, 3 years, 5 years after surgery and the last follow-up, the average improvement rates were (56.0±20.2)%, (65.3±24.0)%, (64.4±25.1)% and (64.3±25.1)%;the disability score decreased by 6.9 (95%CI: 1.4-12.3)points, 8.7 (95%CI: 3.3-14.2)points, 9.0 (95%CI: 3.6-14.5)points, and 9.2 (95%CI: 3.7-14.7) points (all P<0.001), the average improvement rates were (42.9±17.1)%, (55.5±23.2)%, (57.8±24.8)% and (58.7±24.8)%. Patients with DYT1-positive dystonia had higher rates of improvement in movement and disability scores than patients with DYT1-negative, but there was no statistically significant difference. Multiple linear regression analysis showed that gender, age at onset, course of disease, preoperative movement or disability score had no linear relationship with long-term results (improvement rate of movement or disability score) (both P>0.05). Conclusions: STN-DBS is effective and long-lasting in the treatment of isolated dystonia, but no reliable predictor has been found.

[Proximal incisal edge length and recent clinical observation of Siewert type â ¡ advanced esophagogastric junction adenocarcinoma].

Objective: To investigate the clinical effect of the radical resection with a proximal incisal edge length of 20-25 mm and 30-35 mm in Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma, to shorten the minimum safe distance of the proximal incisal edge to 20-25 mm. Methods: A retrospective cohort study method was used. The clinical data of 166 patients with Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma who underwent total gastrectomy from January 2017 to August 2020 in the Department of Gastrointestinal Surgery, Heji Hospital Affiliated to Changzhi Medical College were retrospectively collected. According to the proximal incisal edge length, the patients were divided into two groups: the proximal incisal edge length of 20-25 mm group (69 cases) and 30-35 mm group (97 cases). The perioperative conditions and the 6-month follow-up after the operation were compared between the two groups. Results: There was no statistically significant difference in baseline information between the patients in the two groups (P>0.05). The operations of both groups were completed. The intraoperative operation time of the proximal incisal edge length of 20-25 mm group was shorter than that in the proximal incisal edge length of 30-35 mm group ((172±24)and(206±27)min, P<0.001). There were no significant differences in the amount of intraoperative blood loss, the treatment of the diaphragm during the operation and the positive rate of intraoperative freezing of the upper incisal edge between the patients in the two groups (all P>0.05). And there was no significant differences in the first exhaust time, gastric tube removal time, first feeding time and hospital stay after the operation of the two groups (all P>0.05). There was no significant differences in the incidence of anastomotic leakage, anastomotic stenosis, reflux esophagitis and intestinal obstruction after the operation between the patients in the two groups (all P>0.05). And there was no anastomotic leakage case among the 69 cases in the proximal incisal edge length of 20-25 mm group. Postoperative pathological treatment showed no significant differences in the vascular tumor thrombus and nerve infiltration between the two groups (both P>0.05). During the 6-month follow-up, there was no death or tumor recurrence in the two groups, and there was no significant difference in body weight loss at 6 months after the operation between the two groups (P=0.178). Conclusion: When radical resection of Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma is performed, it is feasible to shorten the minimum safe distance of the proximal incisal edge to 20-25 mm under the premise of ensuring R0 resection. The operation time is shortened. Due to the shortening the incisal edge distance, the anastomotic tension is decreased, and the incidence of postoperative anastomotic leakage is also reduced.

The clinical and molecular significance associated with STING signaling in breast cancer.

STING signaling in cancer is a crucial component of response to immunotherapy and other anti-cancer treatments. Currently, there is no robust method of measuring STING activation in cancer. Here, we describe an immunohistochemistry-based assay with digital pathology assessment of STING in tumor cells. Using this novel approach in estrogen receptor-positive (ER+) and ER- breast cancer, we identify perinuclear-localized expression of STING (pnSTING) in ER+ cases as an independent predictor of good prognosis, associated with immune cell infiltration and upregulation of immune checkpoints. Tumors with low pnSTING are immunosuppressed with increased infiltration of "M2"-polarized macrophages. In ER- disease, pnSTING does not appear to have a significant prognostic role with STING uncoupled from interferon responses. Importantly, a gene signature defining low pnSTING expression is predictive of poor prognosis in independent ER+ datasets. Low pnSTING is associated with chromosomal instability, MYC amplification and mTOR signaling, suggesting novel therapeutic approaches for this subgroup.

[Predictive value of platelet aggregation rate in hemodynamically significant patent ductus arteriosus in preterm infants].

Objective: To explore the predictive value of platelet aggregation rate in patent ductus arteriosus in preterm infants. Methods: This prospective nested case-control study enrolled 72 preterm infants with gestational age<32 weeks, who were admitted to Neonatal Intensive Care Unit of Xuzhou Central Hospital from August 2017 to October 2019. The echocardiography was performed on the 4th to 5th day after birth, and the preterm infants who met the diagnostic criteria of hemodynamically significant patent ductus arteriosus (hsPDA) were included into hsPDA group, and the control group was comprised of matched preterm infants with non-hsPDA according to the proportion of 1∶2. The basic characteristics of the preterm infants were recorded, and their complete blood counts and platelet aggregation function were examined. Clinical data were compared by student's t test and chi-square test between the two groups. The risk factors and their predictive values were analyzed by binary logistic regression analysis and receiver operating characteristic curve. Results: There were 24 preterm infants (16 boys) in the hsPDA group, and 48 (30 boys) in the control group. The incidence of neonatal respiratory distress syndrome (NRDS) grade II-IV in the hsPDA group was higher than that in the control group (67% (16/24) vs. 27% (13/48), χ²=10.422, P=0.001). The thrombocytocrit and adenosine diphosphate-induced platelet aggregation rate in the hsPDA group were lower than those in the control group (0.002 1±0.000 9 vs. 0.002 8±0.000 9, 0.21±0.10 vs. 0.32±0.07, t=-3.043 and -5.093, P=0.004 and <0.01, respectively); while the platelet volume in the hsPDA group was greater than that in the control group ((10.3±2.4) vs. (9.2±2.0) fl, t = 2.713, P = 0.033). The other platelet parameters (platelet count, platelet distribution width, and large platelet ratio) and platelet aggregation rate induced by other inducers (collagen, epinephrine and arachidonic acid) were not significantly different between the two groups (all P>0.05). The low platelet aggregation rate induced by adenosine diphosphate and low thrombocytocrit were independent risk factors for hsPDA in preterm infants (OR=4.525 and 3.994, 95%CI: 1.305-15.689 and 1.143-13.958, respectively). And the adenosine diphosphate-induced platelet aggregation rate had moderate predictive value for hsPDA in preterm infants, as the area under the receiver operating characteristic curve was 0.809, and the cutoff value was 0.245 with 0.67 sensitivity and 0.86 specificity. Conclusions: Poor platelet aggregation function and low thrombocytocrit are independent risk factors for hsPDA in preterm infants with gestational age<32 weeks. Low platelet aggregation rate induced by adenosine diphosphate has moderate predictive value for hsPDA patency.

Metabolic syndrome-related SNPs in HLA and TNF7L2 may be risk factors for generalized pustular psoriasis in Chinese Han population.

Background: Generalized pustular psoriasis (GPP) is a rare and severe type of psoriasis. Previous studies have reported that metabolic syndrome and its components have been associated with psoriasis. Objective: To investigate the association of metabolic syndrome-related single-nucleotide polymorphisms (SNPs) and GPP in Chinese Han population. Materials and Methods: One hundred and thirty-six (136) GPP patients and 965 healthy controls were recruited in the study. Approximately, 4 ml peripheral venous blood was collected from each participant. After collection, second-generation sequencing was used to detect genetic polymorphism of 15 SNPs. The plink 1.07 software package was used for statistical analysis. Results: Rs805303 (p = 0.01, OR = 0.70) and rs3177928 (p = 3.18E-07, OR = 2.66) in HLA were significantly different between the two groups. Moreover, rs4506565 (p = 1.41E-03, OR = 2.72) and rs7901695 (p = 9.39E-04, OR = 2.82) in TCF7L2 were significantly associated with GPP in patients without a previous history of PsV. Genotype analysis of rs4506565 and rs7901695 showed that under the recessive model, genotype frequencies of rs4506565 (p = 0.00, OR = 18.52) and rs7901695 (p = 0.00, OR = 18.44) were significantly different between GPP patients and healthy controls. Conclusion: Rs805303 and rs3177928 in HLA may increase the risk of GPP in the Chinese Han population. TCF7L2 may be a risk factor for GPP in patients without a previous history of PsV.

[Risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis treated with long-term nucleos(t)ide analogues].

Objective: To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs). Methods: The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The (2) test was used for rate comparison. Results: The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion: The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

Mesenchymal stem cells and management of COVID-19 pneumonia.

Human coronavirus, hCoV-19, is highly pathogenic with severe pneumonia associated with rapid virus replication. Arising in Wuhan China December 2019, the current COVID-19 epidemic has rapidly grown with person-to-person infection expanding to become a global health emergency now on pandemic scale. Governments will not be able to minimise both deaths from COVID-19 and the economic impact of viral spread in mitigation of this current COVID-19 pandemic, according to Anderson et al. 2020 [1], Keeping mortality as low as possible will be the highest priority for individuals; hence governments must put in place measures to ameliorate the inevitable economic downturn. The current global picture shows small chains of transmission in many countries and large chains resulting in extensive spread in a few countries, such as Italy, Iran, South Korea, and Japan. Most countries are likely to have spread of COVID-19, at least in the early stages, before any mitigation measures have an impact. The scale of the problem is massive. Here I consider new approaches to improve patient's biological resistance to COVID-19 using stem cells, and how benefit might be scaled and simplified using synthetic stem cells to meet logistical needs within a short time frame.

[Liver histological status and clinic outcome in HBeAg-negative chronic hepatitis B with low viral load].

Objective: To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients. Methods: A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient's clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients. Results: Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion: For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.

Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa.

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary blistering disorder due to a lack of type VII collagen. At present, treatment is mainly supportive. OBJECTIVES: To determine whether intravenous allogeneic bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) are safe in RDEB adults and if the cells improve wound healing and quality of life. METHODS: We conducted a prospective, phase I/II, open-label study recruiting 10 RDEB adults to receive 2 intravenous infusions of BM-MSCs (on day 0 and day 14; each dose 2-4 × 106 cells/kg). RESULTS: BM-MSCs were well tolerated with no serious adverse events to 12 months. Regarding efficacy, there was a transient reduction in disease activity scores (8/10 subjects) and a significant reduction in itch. One individual showed a transient increase in type VII collagen. LIMITATIONS: Open-label trial with no placebo. CONCLUSIONS: MSC infusion is safe in RDEB adults and can have clinical benefits for at least 2 months.