[Regional differences of chronic rhinosinusitis endotypes based on tissue inflammatory and remodeling biomarkers].

Objective: To analyze the characteristics of patients with chronic rhinosinusitis (CRS) in the South China region based on pathological tissue biomarkers for regional comparison. Methods: The study population consisted of CRS in-patients in the First Affiliated Hospital of Sun Yat-sen University from October 2019 to June 2022. Among all the 181 cases, 123 of them were male and 58 were female, with an average age of 40. Retrospectively collected clinical data included demographic information, preoperative symptom scores, preoperative endoscopic images, preoperative paranasal sinus computed tomography scanning images, and inflammatory serological features. In addition, 52 variables of pathological tissue biomarkers including cytokines, chemokines and remodeling factors were collected for analysis. Cluster analysis was performed on the integrated data of training set through centroid-based clustering algorithm, and the inflammatory characteristics, post-operation control status, and airway diseases comorbidity of each endotype were analyzed. R project (version 4.2.2) was used in statistical analysis. Results: Cluster analysis divided 181 patients with CRS into 4 endotypes. Cluster 1 (n=101, 55.80%) showed a locally low inflammatory status. Cluster 2 (n=23, 12.71%) showed a mixed type of inflammation with predominantly neutrophilic inflammation and tissue remodeling. Cluster 3 (n=11, 6.08%) was characterized by type Ⅱ inflammation without tissue remodeling. Cluster 4 (n=46, 25.41%) was mainly characterized by type Ⅱ inflammation with tissue remodeling, showing higher comorbidity rate of asthma and allergic rhinitis. This cluster presented more severe symptoms, significant olfactory dysfunction, extensive overall inflammation based on objective examination results, a notable increase in total eosinophil count and proportion in peripheral blood, and the highest uncontrolled rate observed one year post-surgery. In comparison to other regions, the endotype classification of CRS in Southern China was characterized by a predominant pattern of locally low inflammatory status, a moderate level of type Ⅱ inflammation with tissue remodeling, and a lesser presence of neutrophilic inflammation. Conclusion: CRS distribution in Southern China is mainly characterized by low inflammatory endotype and type Ⅱ inflammation with tissue remodeling. The latter shows more severe clinical manifestations and higher uncontrol rate after surgery.

[Analysis of the efficacy and safety of bone disease treatment in patients with newly diagnosed multiple myeloma treated with denosumab or zoledronic acid].

Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum ß-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

[Effect of SIRT7 on inhibiting the epithelial-mesenchymal transformation in pancreatic cancer cells and related mechanism].

Objective: To investigate the effect and mechanism of SIRT7 in epithelial mesenchymal transformation (EMT) of pancreatic cancer cells. Methods: The pancreatic cancer cells were divided into siControl, siSIRT7, over-expression SIRT7, siSIRT7+siCOL4A1, and siSIRT7+siSLUG groups using siRNA or plasmid transfection. The proliferation, migration and invasion of pancreatic cancer cells were detected by EdU, wound healing assay and Transwell experiments, respectively. The expression of EMT and cancer stem cell (CSC) markers were detected by quantitative real-time reverse transcription polymerase chain reaction assay (qRT-PCR) and western blot. RNA sequencing (RNA-seq) in SIRT7 knockdown PANC-1 cells was performed to explore the signaling pathways and target genes regulated by SIRT7. Then the target genes directly regulated by SIRT7 were identified with quantitative chromatin immunoprecipitation experiment (q-ChIP) and chromatin immunoprecipitation polymerase chain reaction (ChIP-PCR). The expressions of SIRT7 and target genes were detected by immunohistochemical (IHC) in pancreatic cancer tissues, and the correlation between SIRT7 and target gene expression was analyzed using TCGA dataset. The correlation between expression of SIRT7 or target genes and survival was analyzed on KM-plotter website. Finally, GeneMANIA, STRING and ENCORI were used to predict SIRT7-related proteins and miRNAs. Results: EdU assay showed that the cell proliferation rates in SIRT7-overexpressed PANC-1 [(19.33±0.35)%] and BxPC-3 cells [(17.00±1.89)%] were lower than those in the control group [(31.60±1.37)% and (24.33±0.78)%, respectively, P＜0.05]. The proliferation rates of SIRT7-knockdown PANC-1 [(23.94±1.00)% and (27.08±0.97)%] and BxPC-3 cells [(22.00±1.86)% and (25.96±1.61)%] were higher than those of the siControl group [(11.80±1.86)% and (13.42±1.39)%, respectively, P＜0.05]. In PANC-1 cells, the wound healing assay showed that the relative migration rate of SIRT7-overexpression cells [(76.67±2.74)%] was lower than that of control cells [(100.00±2.13)%, P＜0.05]; the relative migration rate of cells with SIRT7 knockdown [(134.22±4.08)% and (199.82±9.20)%, respectively] was higher than that of siControl group [(102.24±3.13)%, P＜0.05]. Compared with the control group, SIRT7 overexpression decreased the number of migrated BxPC-3 cells (45.66±1.69 vs 28.33±2.62, P＜0.05); while SIRT7 knockdown increased these numbers (65.66±2.86 and 82.00±2.94 versus 33.00±0.81, P＜0.01). Transwell experiment revealed that the number of invaded cells in SIRT7 overexpression groups (16.33±2.05 and 34.66±1.69) was lower than that control groups (54.33±4.64 and 58.66±5.90, P＜0.05); with SIRT7 knockdown, the numbers of invaded PANC-1 (63.66±2.49 and 69.33±3.29) and BxPC-3 cells (134.33±3.09 and 181.66±4.02) were higher than those in control groups (35.33±2.49 and 42.00±0.81, P˂0.05). Also, SIRT7 knockdown decreased the expressions of epithelial markers and increased the expressions of mesenchymal and CSC markers. RNA-seq analysis showed that SIRT7 was involved in regulating a variety of cancer-related signaling pathways, including the pancreatic cancer pathway and the EMT pathway. Furthermore, SIRT7 could directly bind to the promoter regions of target genes, such as COL4A1 and SLUG. SIRT7 was negatively correlated with the expression and function of COL4A1 and SLUG in pancreatic cancer cells. The expressions of SIRT7, COL4A1, SLUG and SOX2 were verified in pancreatic cancer tissues by IHC. Finally, SIRT7 was predicted to be associated with many proteins and miRNAs based on GeneMANIA, STRING, and ENCORI online tools. Conclusions: SIRT7 can inhibit the EMT of pancreatic cancer cells through transcriptionally inhibiting the expression of target genes, such as COL4A1 and SLUG. Thus, SIRT7 may serve as a potential tumor suppressor gene in pancreatic cancer.

[Reappraisals of biological behaviors of PDGFRA mutant gastrointestinal stromal tumor].

Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant (P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference (P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant (P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant (P<0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

Can serum IgE or blood eosinophil count predict postoperative oral corticosteroid response in chronic rhinosinusitis with nasal polyps?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by inflammatory mucosa and polyp formation in the paranasal sinuses. The study's primary objective was to evaluate the outcomes of postoperative oral corticosteroid (OCS) in treating patients with bilateral CRSwNP. The secondary objective was to determine whether preoperative serum IgE levels (sIgE)and/or blood eosinophil count (BEC) correlate with postoperative outcomes following OCS use. METHODS: Patients with bilateral CRSwNP (n=236) who underwent endoscopic sinus surgery (ESS) were randomly assigned to receive 15 mg OCS twice daily or a placebo for 2 weeks. We investigated the treatment effects based on the subjective visual analogue scale (VAS), Sino-Nasal Outcome Test 22 (SNOT-22), and objective Lund-Kennedy Endoscopy Score (LKES) over 6 months; subgroups were stratified preoperatively as follows: sIgE <150 IU/mL, sIgE>=150 IU/mL, BEC <0.39x10(9) cells/L, and BEC>=0.39x10(9) cells/L. RESULTS: A total of 193 participants completed the study up to the 6-month follow-up; no apparent linear relationship was noted between sIgE and BEC. No significant differences in scores were noted upon assessment of the VAS, SNOT-22, and LKES among the follow-up timepoints in the primary analysis. However, in the primary or subgroup analyses with sIgE or BEC, significant differences in the longitudinal scores of sleep dysfunction were observed at the 1-month follow-up. CONCLUSION: Postoperative OCS did not significantly affect bilateral CRSwNP outcomes. sIgE levels and BEC may not be surrogate predictive biomarkers to assess the role of postoperative OCS use. OCS may increase the risk of transient sleep disturbance.

LINC01094 promotes human nasal epithelial cell epithelial-to-mesenchymal transition and pyroptosis via upregulating HMGB1.

BACKGROUND: Excessive epithelial-to-mesenchymal transition (EMT) of nasal epithelial cells (NECs) play a prominent role in chronic rhinosinusitis with nasal polyps (CRSwNP) pathogenesis. Long intergenic non-coding RNA 01094 (LINC01094) was previously reported to be overexpressed in CRSwNP, while the regulatory mechanism by which LINC01094 regulates CRSwNP progression remains unclear. Our study aimed to investigate the role of LINC01094 in CRSwNP development. METHODS: hNEC were isolated from tissues of controls and CRSwNP patients and stimulated with interleukin (IL)-13. 3-(4, 5-Dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay was employed to analyze hNEC viability. Flow cytometry was employed to analyze pyroptosis. Immunofluorescence was employed to analyze Snail nuclear translocation. The interactions between LINC01094, fused in sarcoma (FUS) and high mobility group box-1 (HMGB1) were analyzed by RNA immunoprecipitation (RIP) and RNA pull-down assays. RESULTS: LINC01094 and EMT-related proteins were markedly upregulated in nasal polyp tissues of CRSwNP. LINC01094 knockdown inhibited IL-13-induced hNEC EMT and pyroptosis. LINC01094 promoted HMGB1 expression in CRSwNP by binding with FUS. HMGB1 promoted Snail nuclear import in GSK-B phosphorylation-dependent manner. CONCLUSION: LINC01094 facilitated hNEC EMT and pyroptosis in CRSwNP by activating the HMGB1/GSK-B Snail axis, which suggested that LINC01094 might serve as a biomarker and therapeutic target in CRSwNP.

[Effects of free gracilis muscle flap combined with sural nerve transfer for reconstruction of digital flexion and sensory function of hand in patient with wrist electric burn].

Objective: To explore the effects of free gracilis muscle flap combined with sural nerve transfer for reconstruction of digital flexion and sensory function of hand in patient with severe wrist electric burn. Methods: A retrospective observational study was conducted. From January 2017 to December 2020, 4 patients with wrist high-voltage electric burn admitted to the Department of Burns of the First People's Hospital of Zhengzhou and 4 patients with wrist high-voltage electric burn admitted to the Department of Hand Surgery of Beijing Jishuitan Hospital met the inclusion criteria, including 6 males and 2 females, aged 12 to 52 years. They were all classified as type Ⅱ wrist high-voltage electric burns with median nerve defect. In the first stage, the wounds were repaired with free anterolateral thigh femoral myocutaneous flap. In the second stage, the free gracilis muscle flap combined with sural nerve transplantation was used to reconstruct the digital flexion and sensory function of the affected hand in 3 to 6 months after wound healing. The cut lengths of muscle flap and nerve were 32 to 38 and 28 to 36 cm, respectively. The muscle flap donor area and nerve donor area were both closed and sutured. The survival condition of gracilis muscle flap and sural nerve, the wound healing time of recipient area on forearm, the healing time of suture in muscle flap donor area and nerve donor area were observed and recorded after operation, and the recovery of donor and recipient areas was followed up. In 2 years after operation, the muscle strength of thumb and digital flexion and finger sensory function after the hand function reconstruction were evaluated with the evaluation criteria of the hand tendon and nerve repair in the trial standard for the evaluation of functions of upper limbs of Hand Surgery Society of Chinese Medical Association. Results: All the gracilis muscle flap and sural nerve survived successfully after operation. The wound healing time of recipient area on forearm was 10 to 14 days after operation, and the healing time of suture in muscle flap donor area and nerve donor area was 12 to 15 days after operation. The donor and recipient areas recovered well. In the follow-up of 2 years after operation, the muscle strength of thumb and digital flexion was evaluated as follows: 4 cases of grade 5, 3 cases of grade 4, and 1 case of grade 2; the finger sensory function was evaluated as follows: 4 cases of grade S3+, 2 cases of grade S3, and 2 cases of grade S2. Conclusions: For patients with hand dysfunction caused by severe wrist electric burn, free gracilis muscle flap combined with sural nerve transplantation can be used to reconstruct the digital flexion and sensory function of the affected hand. It is a good repair method, which does not cause great damage to thigh muscle flap donor area or calf nerve donor area.

[Curative effects of ultrathin anterolateral femoral flap in one-stage split-finger repair of palmar combined with multiple finger wounds].

Objective: To explore the curative effects of ultrathin anterolateral femoral flap in one-stage split-finger repair of palmar combined with multiple finger wounds. Methods: A retrospective observational study was conducted. From October 2016 to June 2018, 20 patients with wounds on palms and multiple fingers who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 15 males and 5 females, aged 18 to 77 years. After debridement, the wound area was 8 cm×4 cm-17 cm×12 cm. The wound was repaired by ultrathin anterolateral femoral flap with area of 9 cm×5 cm to 19 cm×13 cm. According to the wound condition of finger, the finger division was performed in one stage, and the length-to-width ratio of the split-finger flap was 2.0:1.0-2.5:1.0. During the surgery, the descending branches of lateral circumflex femoral artery and accompanying vein of flap were anastomosed end-to-end to the radial artery and vein in the recipient area, respectively, and the anterolateral femoral cutaneous nerve of flap was bridged with the superficial branch of radial nerve in the recipient area. The wounds in the donor area of flap in 14 patients were sutured directly, the wounds in the donor area of flap in 3 patients were repaired by relay superficial iliac circumflex artery perforator flap, and the wounds in the donor area of flap in 3 patients were covered by free trunk medium-thick skin graft. The survival of flap, occurrence of vascular crisis and other complications, and healing of wounds in the donor area of flap were recorded. The appearance of flap, scar hyperplasia in the donor and recipient areas and the patients' satisfaction with the shape and function of the donor and recipient areas were followed up. In 1 year after surgery, the two-point discrimination distance of the flap was measured, and the recovery of hand function was evaluated by the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association. Results: The flaps of 17 patients survived without vascular crisis or other complications after surgery. The flap of 1 patient had poor blood circulation and partial necrosis, and the wound was healed 14 days after dressing change and grafting of split-thickness skin graft from head. Two patients had mild cyanosis at the margin of flap after surgery, which disappeared spontaneously 5 days later. Incisions at donor site, relay flaps, and skin grafts of all patients survived well. After surgery, the color and texture of flap were basically the same as that of the normal skin of hand, and linear scars were observed in the donor and recipient areas. The patients were satisfied with the recovery of appearance and function of donor and recipient areas. After 1 year of follow-up, the patients' hand sensory function recovered well, the two-point discrimination distance of flap was 4-6 mm, and the recovery of hand function was evaluated as excellent in 18 cases and good in 2 cases. Conclusions: The ultrathin anterolateral femoral flap in repairing the palmar combined with multiple finger wounds in one-stage split-finger can significantly reduce the number of surgeries and improve the function and beauty of the hand, so it is worthy of clinical promotion.

[Clinical efficacy of local injection of platelet-rich plasma combined with double-layer artificial dermis in treating wounds with exposed tendon on extremity].

Objective: To investigate the clinical efficacy of local injection of platelet-rich plasma (PRP) combined with double-layer artificial dermis in treating wounds with exposed tendon on extremity. Methods: A retrospective observational study was conducted. From December 2017 to October 2022, 16 patients were admitted to Department of Orthopaedic Trauma of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, and 32 patients were admitted to Department of Burns and Plastic Surgery of Guiyang Steel Factory Staff Hospital. All the patients had wounds with exposed tendon on extremity caused by various reasons and met the inclusion criteria. There were 39 males and 9 females, aged 26 to 58 years. The patients were divided into PRP alone group, artificial dermis alone group, and PRP+artificial dermis group, with 16 patients in each group. The wounds were treated with autologous PRP, double-layer artificial dermis, or thei combination of autologous PRP and double-layer artificial dermis, followed by autologous split-thickness scalp grafting after good growth of granulation tissue. On the 7th day after the secondary surgery, the autograft survival was observed, and the survival rate was calculated. The wound healing time and length of hospital stay of patients were recorded. At 3 and 6 months after wound healing, the Vancouver scar scale (VSS) was used to score the pigmentation, height, vascularity, and pliability of scars, and the total score was calculated. Adverse reactions during the entire treatment process were recorded. Data were statistically analyzed with chi-square test, Fisher's exact probability test, one-way analysis of variance, least significant difference test, Kruskal-Wallis H test, Nemenyi test, and Bonferroni correction. Results: On the 7th day after the secondary surgery, there was no statistically significant difference in the autograft survival rate of patients among PRP alone group, artificial dermis alone group, and PRP+artificial dermis group (P>0.05). The wound healing time and length of hospital stay of patients in PRP+artificial dermis group were (20.1±3.0) and (24±4) d, respectively, which were significantly shorter than (24.4±5.5) and (30±8) d in PRP alone group (P<0.05) and (24.8±4.9) and (32±8) d in artificial dermis alone group (P<0.05). At 3 and 6 months after wound healing, the pliability scores of patients in PRP+artificial dermis group were significantly lower than those in PRP alone group (with Z values of 12.91 and 15.69, respectively, P<0.05) and artificial dermis alone group (with Z values of 12.50 and 12.91, respectively, P<0.05). There were no statistically significant differences in pigmentation, vascularity, height scores, and total score of scar of patients among the three groups (P>0.05). In artificial dermis alone group, one patient experienced partial liquefaction and detachment of the double-layer artificial dermis due to local infection of Staphylococcus epidermidis, which received wound dressing change, second artificial dermis transplantation, and subsequent treatment as before. No adverse reactions occurred in the remaining patients during the whole treatment process. Conclusions: Local injection of PRP combined with double-layer artificial dermis is effective in treating wounds with exposed tendon on extremity, which can not only significantly shorten wound healing time and length of hospital stay, but also improve scar pliability after wound healing to some extent in the long term. It is a clinically valuable treatment technique that is worth promoting and applying.

[A randomized controlled study on the long-term efficacy of intra-cervical lymphatic immunotherapy for adult allergic rhinitis].

Objective: To determine the long-term efficacy and safety of intra-cervical lymphatic immunotherapy (ICLIT) for adult allergic rhinitis (AR) by comparing it with subcutaneous immunotherapy (SCIT). Methods: A total of 100 adult AR patients with dust mite allergy in Department of Otorhinolaryngology, First People's Hospital of Foshan from Feb 2018 to Dec 2019 were randomly divided into two groups, 50 in SCIT group [including 42 males and 8 females, aging (32.55±9.72) years] and 50 in ICLIT group [including 45 males and 5 females, aging (31.33±9.84) years]. The changes in total symptom score (total system score, TSS), nasal symptom score (total nasal symptom score, TNSS), eye symptom score (total ocular scoring system, TOSS), drug score (total medication score, TMS), and quality of life score of the two groups of patients were evaluated before and after treatment, and the adverse reactions of all patients during the treatment period were recorded. The changes in the level of dust mite specific IgE (sIgE) in the serum were evaluated. GraphPad Prism 9.0 software was used for statistical analysis. Results: In the SCIT group, 38 patients completed treatment and follow-up, with a dropout rate of 24%. In the ICLIT group, 48 patients completed treatment and follow-up, with a dropout rate of only 4%. The scores of TSS, TNSS, TOSS, TMS, and quality of life in the ICLIT group before treatment were 32.1±3.0, 27.3±3.1, 4.8±2.8, 2.3±0.9, and 68.1±28.7, respectively; After 36 months of treatment, the scores were 21.8±11.4, 18.1±9.4, 3.7±2.9, 1.3±1.1, and 36.0±26.7, respectively, which were significantly lower than those before treatment (all P<0.001). After 36 months of treatment, the TSS of the ICLIT group improved by 10.3±11.2 compared to before, while the TSS of the SCIT group improved significantly by 21.9±11.0 compared to before, with statistically significant differences between the groups (P<0.001). No serious systemic adverse reactions occurred in both groups of patients. Conclusions: ICLIT treatment for adult AR has long-term efficacy, high safety, and high compliance, but its long-term efficacy is not as good as SCIT. ICLIT can be considered as a new complementary option for AR immunotherapy.

[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma].

Objective: This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) . Methods: A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model. Results: The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions: PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for T lymphoblastic leukemia/lymphoma].

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.

[Effects and clinical significance of NLRP3 inflammasome activated by IL-17A in CRSwNP].

Objective: To investigate the effects and clinical significance of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activated by interleukin (IL)-17A in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021 were collected, including 28 CRSwNP (including 19 males and 9 females, aged 19 to 67 years), 22 chronic rhinosinusitis without nasal polyps (CRSsNP) and 22 controls. qRT-PCR was used to detect the expressions of IL-17A, NLRP3, IL-1ß and IL-18 in the three groups, and their correlations were analyzed. The positions of IL-17A, NLRP3 and IL-18 in nasal polys were analyzed by immunofluorescence. Western Blotting and ELISA were employed to detect the expression of NLRP3, IL-1ß and IL-18 in the human nasal epithelial cells after using IL-17A stimulation or IL-17A receptor inhibitor. Immunofluorescence was used to observe the NLRP3, IL-1ß, and IL-18 protein expression after IL-17A stimulating human nasal epithelial cells, and after the use of IL-17A receptor inhibitor and NLRP3 inhibitor MCC950. The correlations between NLRP3, IL-1ß, IL-18 and CT scores, nasal endoscopic scores, visual analogue scale (VAS) scores, and sino-nasal outcome test (SNOT) 22 scores of CRSwNP patients were analyzed. SPSS 20.0 software was used for statistical analysis. Results: The expressions of IL-17A, NLRP3, IL-1ß and IL-18 in the tissues of CRSwNP patients were significantly higher than those in CRSsNP group(P=0.018,P<0.001,P=0.005, P=0.016) and the control group(all P<0.001). IL-17A was positively correlated with the expression of NLRP3, IL-1ß, and IL-18(r ralue was 0.643,0.650,0.629,respectively, all P<0.05). IL-17A, NLRP3, and IL-18 were co-localized in the epithelial propria of polyp tissue. IL-17A stimulated the expressions of NLRP3, IL-1ß, and IL-18 in human nasal epithelial cells. After the use of IL-17A receptor inhibitor, the expressions of NLRP3, IL-1ß, and IL-18 were significantly down-regulated. After the use of NLRP3 inhibitor MCC950, IL-17A was significantly down-regulated to promote the expression of NLRP3, IL-1ß, and IL-18. The expressions of NLRP3, IL-1ß and IL-18 were positively correlated with CT, nasal endoscopy, VAS, and SNOT22 scores in patients with CRSwNP. Conclusions: IL-17A promotes the release of IL-1ß and IL-18 by activating the NLRP3 inflammasome and aggravates the severity of the disease in CRSwNP.

[Gray zone lymphoma: five cases report and literature review].

Objective: To investigate the clinical and pathological features, treatment, and prognosis of gray zone lymphoma (GZL) . Methods: From July 2, 2013, to February 10, 2021, the clinical and pathological features, treatment, and outcomes of five patients with GZL at the Blood Diseases Hospital, Chinese Academy of Medical Sciences were studied retrospectively. Results: There were one male and 4 females, with a median age of 28 (16-51) years at diagnosis. Four patients had mediastinal (thymic) involvement, two of which had superior vena cava obstruction syndrome, and 3 patients had extra-nodal involvement. There was one case with a limited Ann Arbor stage and 4 cases with a progressive stage. Three patients had cHL-like pathomorphology with scattered Hodgkin-like cells, strongly positive for CD20, positive for CD30, and CD15 was negative; the other two patients had both cHL and DLBCL morphology, with some areas resembling Hodgkin cells and some areas resembling immunoblasts, strongly positive for CD30, and CD15 but negative CD20. Two patients were treated with cHL-like regimens for induction and achieved only partial remission; after salvage therapy with enhanced DLBCL-like regimens, all achieved complete remission (CR) . Three patients were treated with enhanced DLBCL-like immunochemotherapy regimens for induction, and two patients were effective, one of whom achieved CR. Four patients who did not achieve CR were given second or third-line salvage therapy, and all of them recovered. One patient lost parity, one died of disease progression at 35.9 months after diagnosis, and the remaining three maintained sustained remission. Conclusions: GZL is uncommon, usually affects younger patients, is mediastinal and is diagnosed using path morphology and immunophenotype. Patients with newly diagnosed GZL appear to be more sensitive to DLBCL-like immunochemotherapy regimens; relapsed or refractory patients were tended with non-cross-resistant combination chemotherapy or with new drugs.

Different dexamethasone doses in the perioperative period improve short-term outcomes of total hip arthroplasty: a randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the efficacy of different dexamethasone doses in the perioperative period of total hip arthroplasty (THA). PATIENTS AND METHODS: We randomly divided 180 patients into three groups: three perioperative saline injections (Group A, placebo); two perioperative doses of 15 mg dexamethasone plus a postoperative saline injection at 48 h (Group B); and three perioperative doses of dexamethasone (10 mg) (Group C). Primary outcomes were postoperative pain at rest and while walking. We also recorded consumption of analgesics and antiemetics, incidence of postoperative nausea and vomiting (PONV), C-reactive protein (CRP) and interleukin-6 (IL-6) levels, postoperative length of stay (p-LOS), range of motion (ROM), nausea, Identity-Consequence-Fatigue-Scale (ICFS), and severe complications (e.g., incidence of surgical site infection, SSI and gastrointestinal bleeding, GIB). RESULTS: Group B and C had significantly lower pain scores at rest than Group A on postoperative day 1. Group B and C also had significantly lower dynamic pain score, CRP, and IL-6 than Group A on postoperative day 1, 2, and 3. Patients in Group B and C had lower PONV incidence, reduced use of analgesics and antiemetics, improved ROM, shorter p-LOS, lower VAS nausea score, and lower ICFS than Group A patients. On postoperative day 3, patients in Group C had significantly lower dynamic pain and ICFS scores, IL-6, and CRP than Group B patients, as well as higher ROM. None of the groups exhibited SSI or GIB. CONCLUSIONS: Dexamethasone provides short-term advantages in reducing pain, PONV, inflammation, and ICFS, and increasing ROM in the early postoperative period after THA. Dexamethasone efficacy in reducing post-THA pain, inflammation, and PONV at 10 mg and 15 mg is similar during the first 48 h. Dexamethasone (30 mg) divided into three 10 mg doses was superior to two doses (15 mg) in reducing pain, inflammation, and ICFS, as well as in increasing ROM on postoperative day 3.