OBJECTIVE: To retrospectively analyze the characteristics and influencing factors of COVID-19 infection in patients with multiple myeloma (MM) who underwent autologous hematopoietic stem cell transplantation (AHSCT). METHODS: The clinical data of MM patients who underwent AHSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 26, 2021 to December 26, 2022 were collected. The onset of COVID-19 infection, corresponding symptoms and laboratory tests were followed up in outpatient or by the means of telephone contact and online questionnaires. Related analysis was then performed. RESULTS: This study included 96 patients, and 72 cases among them were infected with COVID-19 while 24 cases were uninfected. Logistic regression analysis showed that vaccination did not significantly reduce the risk of COVID-19 infection, but patients who received two doses of the vaccine had a lower risk of developing moderate and severe disease than those who did not receive or received one dose (OR =0.06, P =0.029). Patients who received daratumumab before had a higher risk of COVID-19 infection (OR =5.78, P =0.039), while those with a history of immunomodulatory drugs (IMiDs) had the opposite effect (OR =0.31, P =0.028). The use of both drugs did not affect the severity of COVID-19 infection. CONCLUSION For MM patients undergoing AHSCT as first-line chemotherapy, COVID-19 vaccination does not significantly reduce the infection rate, but it plays a role in preventing moderate and severe cases. The application of antineoplastic drugs with different mechanisms has a certain impact on the susceptibility to the COVID-19, which should be considered comprehensively when creating treatment plans.
Humans ; Multiple Myeloma/complications* ; COVID-19/epidemiology* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Adult ; Antibodies, Monoclonal

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Congenital infiltrating lipomatosis of the face (CIL-F) represents a rare lipomatous lesion, as evidenced by a case admitted to the Department of Plastic and Reconstructive Surgery at the Second Affiliated Hospital of Kunming Medical University in August 2023. The patient, a 7-year-old male, presented with diffuse enlargement of the right middle and lower face and a forehead mass since birth. Imaging assessments including CT scan with three dimensional reconstruction and MRI revealed infiltrative fatty growth in the right middle and lower face, abnormal subcutaneous fat hyperplasia in the forehead, and asymmetric abnormal hyperplasia of the right mandible. Following surgical resection, genetic testing of the excised tissue identified a mutation of the PIK3CA gene. Remarkably, the patient demonstrated satisfactory recovery six months post-surgery. Given its rarity in clinic, this case offers valuable clinical insights for managing similar disease.

In recent years, intratumoral immune injection, as an emerging drug delivery modality in the treatment of advanced malignant tumors, has not only improved drug bioavailability, but also reduced systemic toxicity by injecting bacteria and toxins, oncolytic viruses, cytokines, monoclonal antibodies, immune cells, pattern recognition receptor agonists, chemotherapeutic agents, mRNA, and antibody-drug conjugates into solid tumors. In addition, the development of drug delivery carriers such as iodized oil, hydrogel, nanoparticles and drug-carrying microspheres has solved the problem that drugs injected intratumorally are prone to diffuse through the vascular system and are difficult to remain locally for a long period of time. An in-depth exploration of the research progress of intratumoral immune injection of drugs and drug delivery carriers can provide a reference for further research on intratumoral immune injection, and improve the clinical benefits for patients with solid tumors.

Objective Vascular dementia(VD)is a common cognitive dysfunction associated with cerebrovascular disease.This study is aimed at investigating the therapeutic effect of anisodine hydromide(AH)on VD and the potential antioxidative stress mechanisms involved.Methods A VD model was established in Sprague-Dawley(SD)rats through permanent bilateral common carotid artery occlusion.The rats were divided into a sham group,a VD model group,and AH treatment groups receiving AH at low,medium,or high doses(n=4).The neurological function of the rats in each group was evaluated using the Bederson scale,and limb coordination ability was assessed using the pole climbing test.Superoxide dismutase(SOD)and malondialdehyde(MDA)levels in the serum and brain were measured by enzyme-linked immunosorbent assay(ELISA)to assess the level of oxidative stress.In addition,apoptosis was assessed by TUNEL assay,and reactive oxygen species(ROS)levels in neuronal cells were determined using dichloro-dihydro-fluorescein diacetate(DCFH-DA)probe.The potential mechanism of action of AH on M receptors was investigated using M1-M5 inhibitors.Results Compared with the sham group,the nerve function and limb coordination of rats in the VD model group were significantly impaired(P＜0.01),and the SOD levels were significantly decreased in the serum([100.70±18.95]U/mL vs.[44.22±7.11]U/mL,P＜0.001)and the brain([131.77±8.34]U/mg vs.[84.39±4.10]U/mg,P＜0.01),MDA levels were significantly increased in the serum([12.03±1.01]nmol/mL vs.[17.74±1.00]nmol/mL,P＜0.001)and the brain([4.41±0.30]nmol/mg vs.[6.17±0.70]nmol/mg,P＜0.05).AH treatment significantly improved the neurological function and limb coordination ability of VD rats.In comparison with the VD group,the high-dose AH treatment group,in particular,exhibited the most significant increase in SOD levels in the serum([44.22±7.11]U/mL vs.[98.67±0.86]U/mL,P＜0.001)and the brain([84.39±4.10]U/mg vs.[162.83±17.36]U/mg,P＜0.001),and the most significant decrease in MDA levels in the serum([17.74±1.00]nmol/mL vs.[6.68±0.06]nmol/mL,P＜0.001)and the brain([6.17±0.70]nmol/mg vs.[3.96±0.77]nmol/mg,P＜0.01).AH also reduced the number of TUNEL positive cells(P＜0.01)in a dose-dependent manner.The percentage of apoptotic cells was(36.10±9.07)％,(9.60±5.63)％,and(3.43±0.92)％,respectively,for AH treatment at low,medium,and high concentrations,indicating that AH had an inhibitory effect on apoptosis.According to findings from the in vitro experiments,AH treatment reduced the MDA content(P＜0.01),increased the SOD activity(P＜0.01),and decreased the ROS levels of HT22 and NSC-34 cells in a dose-dependent manner.M2 receptor inhibitors could reduce the ROS level in oxidative stress injury,suggesting that AH,as an M receptor antagonist,might exert its effect by inhibiting the M2 receptor.Conclusion AH modulates SOD and MDA levels and reduces oxidative stress injury,thereby improving neurological function and limb coordination and showing potential therapeutic effects in VD.The neuroprotective effects of AH may be related to its antioxidative stress and antiapoptotic mechanisms,and the M2 receptor may be a potential target of its actions.These findings provide an important theoretical basis for the development of new therapeutic strategies for VD.

Objective:To investigate the prognostic value of serum chloride ion concentration in critically ill or clinically stable pa-tients with decompensated cirrhosis.Methods:A retrospective study was conducted among the patients with decompensated cirrhosis who attended the intensive care unit(ICU)and Department of Gastroenterology,The First Hospital of Lanzhou University,from Janu-ary 2017 to January 2022,and the patients were divided into ICU cohort and Gastroenterology cohort.The outcome event for the ICU cohort was in-hospital death.A logistic regression analysis was used to investigate the association between serum chloride levels and ICU mortality rate;the receiver operating characteristic(ROC)curve was plotted and the area under the ROC curve(AUC)was calcu-lated to assess the value of blood chloride level in predicting ICU mortality rate.The patients in the Gastroenterology cohort were fol-lowed up with the outcome event of all-cause mortality rate,and the Cox regression analysis and the Kaplan-Meier analysis were used to investigate the value of blood chloride level in predicting mortality rate.Results:In the ICU cohort,serum chloride ion was signifi-cantly associated with in-hospital mortality in the ICU(odds ratio=0.934,95%CI=0.871-0.993,P=0.035),and blood chlorine had an AUC of 0.687 in predicting in-hospital mortality in the ICU.In the Gastroenterology cohort,serum chloride ion concentration was sig-nificantly associated with mortality rate in the subgroup with a Child-Pugh score of<10(hazard ratio=0.906,95%CI=0.822-0.997,P=0.043),and hypochloremia was associated with a lower survival rate.Conclusion:Hypochloremia is associated with the increase in mortality rate in patients with decompensated cirrhosis.

Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.

Objective:To explore the efficacy and its related factors of rituximab (RTX) in the treatment of children with frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS).Methods:It was a single-center retrospective study. The clinical data of FRNS/SDNS children first treated with RTX in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2016 to September 1, 2023 were collected. The number of relapse within 1 year before and after RTX treatment, the time to first relapse after RTX treatment, and the time to B-cell reconstitution were analyzed. At the first treatment, a single dose of RTX was given at 375 mg/m 2, with a maximum dose of 500 mg, once a week, for 1 to 4 doses. The count of CD19 + lymphocytes in the peripheral blood of the children was continuously monitored. If B-cell reconstruction was performed, the decision on whether to proceed to the next course of RTX treatment was made based on clinical manifestations. Kaplan-Meier method was used to analyze relapse-free survival rate after receiving RTX. Cox proportional hazards regression model was used to analyze the related factors of relapse after RTX treatment. Results:A total of 98 FRNS/SDNS children receiving RTX treatment were enrolled, including 75 males (76.5%). The age at onset was 4.0 (1.9, 7.1) years and age of receiving RTX was 11.3 (8.5, 13.5) years. There were 90 children (91.8%) achieving complete remission, while 8 patients (8.2%) did not respond to RTX treatment, and 3 patients (3.1%) progressed to end-stage kidney disease after receiving RTX. The relapse-free survival rates at 6 months and 1 year after RTX treatment were 83.3% (75/90) and 57.9% (22/38), respectively. The frequency of relapse 1 year after RTX treatment decreased compared to 1 year before RTX treatment ( Z=-7.398, P<0.001). Compared with children without relapse during the period of B-cell depletion, relapsed children had a higher number of relapse within one year after RTX treatment ( Z=5.246, P<0.001). The time to first relapse after RTX treatment was 8.3 (4.6, 13.9) months in 51 relapse patients. Compared with children receiving 1 dose of RTX in the first course, those receiving 2 or more doses had a longer time to the first relapse ( Z=2.983, P=0.003). There was no statistically significant difference in time to the first relapse between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). The reconstruction time of B cells after the first course of RTX was 6.9 (5.3, 9.0) months. Compared to children receiving one dose of RTX in the first course, those receiving two or more doses had a longer B-cell reconstitution time ( Z=2.739, P=0.006). There was no statistically significant difference in B-cell reconstitution time between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). Univariate Cox regression analysis showed that recurrence after calcineurin inhibitor (CNI) treatment before RTX treatment and the number of recurrence in one year before RTX treatment were correlated factors of recurrence after RTX treatment (both P<0.05). Multivariate Cox regression analysis showed that recurrence after CNI treatment before RTX treatment was an independent correlated factor of relapse after RTX therapy ( HR=3.496, 95% CI 1.245-9.818, P=0.018). Infusion reactions occurred in 10 patients (10.2%) and infections were observed in 24 patients (24.5%) during B cell depletion. No serious adverse events occurred. Conclusions:RTX is well tolerated and effective in treating FRNS/SDNS. Recurrence after CNI treatment before RTX treatment may be an independent related factor of relapse after RTX treatment.

Congenital infiltrating lipomatosis of the face (CIL-F) represents a rare lipomatous lesion, as evidenced by a case admitted to the Department of Plastic and Reconstructive Surgery at the Second Affiliated Hospital of Kunming Medical University in August 2023. The patient, a 7-year-old male, presented with diffuse enlargement of the right middle and lower face and a forehead mass since birth. Imaging assessments including CT scan with three dimensional reconstruction and MRI revealed infiltrative fatty growth in the right middle and lower face, abnormal subcutaneous fat hyperplasia in the forehead, and asymmetric abnormal hyperplasia of the right mandible. Following surgical resection, genetic testing of the excised tissue identified a mutation of the PIK3CA gene. Remarkably, the patient demonstrated satisfactory recovery six months post-surgery. Given its rarity in clinic, this case offers valuable clinical insights for managing similar disease.

Objective:To explore the efficacy and its related factors of rituximab (RTX) in the treatment of children with frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS).Methods:It was a single-center retrospective study. The clinical data of FRNS/SDNS children first treated with RTX in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2016 to September 1, 2023 were collected. The number of relapse within 1 year before and after RTX treatment, the time to first relapse after RTX treatment, and the time to B-cell reconstitution were analyzed. At the first treatment, a single dose of RTX was given at 375 mg/m 2, with a maximum dose of 500 mg, once a week, for 1 to 4 doses. The count of CD19 + lymphocytes in the peripheral blood of the children was continuously monitored. If B-cell reconstruction was performed, the decision on whether to proceed to the next course of RTX treatment was made based on clinical manifestations. Kaplan-Meier method was used to analyze relapse-free survival rate after receiving RTX. Cox proportional hazards regression model was used to analyze the related factors of relapse after RTX treatment. Results:A total of 98 FRNS/SDNS children receiving RTX treatment were enrolled, including 75 males (76.5%). The age at onset was 4.0 (1.9, 7.1) years and age of receiving RTX was 11.3 (8.5, 13.5) years. There were 90 children (91.8%) achieving complete remission, while 8 patients (8.2%) did not respond to RTX treatment, and 3 patients (3.1%) progressed to end-stage kidney disease after receiving RTX. The relapse-free survival rates at 6 months and 1 year after RTX treatment were 83.3% (75/90) and 57.9% (22/38), respectively. The frequency of relapse 1 year after RTX treatment decreased compared to 1 year before RTX treatment ( Z=-7.398, P<0.001). Compared with children without relapse during the period of B-cell depletion, relapsed children had a higher number of relapse within one year after RTX treatment ( Z=5.246, P<0.001). The time to first relapse after RTX treatment was 8.3 (4.6, 13.9) months in 51 relapse patients. Compared with children receiving 1 dose of RTX in the first course, those receiving 2 or more doses had a longer time to the first relapse ( Z=2.983, P=0.003). There was no statistically significant difference in time to the first relapse between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). The reconstruction time of B cells after the first course of RTX was 6.9 (5.3, 9.0) months. Compared to children receiving one dose of RTX in the first course, those receiving two or more doses had a longer B-cell reconstitution time ( Z=2.739, P=0.006). There was no statistically significant difference in B-cell reconstitution time between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). Univariate Cox regression analysis showed that recurrence after calcineurin inhibitor (CNI) treatment before RTX treatment and the number of recurrence in one year before RTX treatment were correlated factors of recurrence after RTX treatment (both P<0.05). Multivariate Cox regression analysis showed that recurrence after CNI treatment before RTX treatment was an independent correlated factor of relapse after RTX therapy ( HR=3.496, 95% CI 1.245-9.818, P=0.018). Infusion reactions occurred in 10 patients (10.2%) and infections were observed in 24 patients (24.5%) during B cell depletion. No serious adverse events occurred. Conclusions:RTX is well tolerated and effective in treating FRNS/SDNS. Recurrence after CNI treatment before RTX treatment may be an independent related factor of relapse after RTX treatment.