177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

Objective: The study investigated the efficacy and safety of daratumumab in the treatment of cardiac light chain (AL) amyloidosis. Methods: We retrospectively analyzed the clinical characteristics, hematologic response, organ response, long-term survival, and adverse events of 20 patients with newly diagnosed or relapsed/refractory cardiac AL amyloidosis treated with daratumumab in Peking Union Medical College Hospitalo from January 2017 to March 2021. Results: The overall median age of 20 patients was 62 (range, 45-73) yeas, with a male to female ratio of 2.3:1. Nine patients were newly diagnosed, while 11 patients had relapsed or refractory disease. Based on Mayo 2004 cardiac AL staging system, stages Ⅱ and Ⅲ diseases were present in 20 patients respectively. Four patients died during the first cycle of daratumumab, and the remaining 16 patients completed a median of 3 (range, 1-10) cycles of treatment. Overall hematologic response rates were 80% each at 1, 3, and 6 months after treatment initiation, and 45% , 60% , and 60% of the patients achieved at least a very good partial response at 1, 3, and 6 months respectively. The median duration to hematologic response was 13 (range, 6-28) days. At 3, 6, and 12 months, 20% , 30% , and 40% of the patients respectively achieved a cardiac response, and the median days to response was 91 (range, 30-216) days. As of the last follow-up, 9 (45% ) patients died. The 1-month mortality rate of all the patients and stage IIIb patients was 25% and 40% , respectively. The 1-year overall survival rate was 48.4% . Lymphocytopenia was the most common hematological adverse event (above grade 3) . Non-hematological adverse events were mainly infusion-related reactions and infections. Conclusion: Daratumumab could induce deep and rapid hematologic response in newly diagnosed and previously treated cardiac AL amyloidosis patients. However, daratumumab was not effective in preventing the high and early mortality rate in stage Ⅲb patients.
Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Humans ; Immunoglobulin Light-chain Amyloidosis/drug therapy* ; Male ; Retrospective Studies ; Treatment Outcome

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Antibody-drug conjugates (ADCs) are one of the most important classes of anticancer therapeutics. Human epidermal growth factor receptor-2 (HER2), which is highly expressed in many types of aggressive cancers including breast and ovarian cancer, has been approved as an ideal target for ADCs. Lidamycin (LDM), developed by Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, is an enediyne-containing antibiotic with potent anti-tumor activity. LDM is a promising payload for ADCs. In the present research, using a special site-directed conjugating technology, we made a novel ADC (607-LDM) with a drug-to-antibody ratio (DAR) of 2 and composed of the anti-HER2 antibody 607 and LDM. The new ADC exhibited potent antitumor activity against human ovarian cancer SKOV3 and breast cancer BT-474 cells. It also induced apoptosis and G2/M arrest. In nude mice with SKOV3 xenografts and a tumor volume of 150-200 mm³, a single intravenous injection 607-LDM at 1 mg·kg^-1 induced tumor growth inhibition of 72.4%, which was significant compared to either LDM (50.6%) or antibody (30.2%) treatment alone, or both in combination (50.1%, P < 0.05). All animal experiments were performed in accord with National Regulations and approved by the Animal Experiments Ethical Committee of College of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences. The novel ADC designed in this study, 607-LDM, is a promising candidate for the treatment of HER2-positive cancers.

OBJECTIVE: Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19. METHODS: A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored. RESULTS: COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3 CONCLUSION Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3
Adult ; Antiviral Agents/therapeutic use* ; COVID-19/pathology* ; Capsules ; DNA, Viral/analysis* ; Drugs, Chinese Herbal/therapeutic use* ; Feces/virology* ; Female ; Humans ; Length of Stay ; Lymphocyte Count ; Male ; Medicine, Chinese Traditional/methods* ; Middle Aged ; Retrospective Studies ; SARS-CoV-2/genetics* ; Severity of Illness Index ; Treatment Outcome ; Young Adult

OBJECTIVE: To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action. METHODS: A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups. RESULTS: The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044). CONCLUSION In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.
Adult ; Aged ; COVID-19/drug therapy* ; Female ; Humans ; Length of Stay ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Retrospective Studies ; SARS-CoV-2

Objective:To investigate the clinical features and outcomes of patients with light-chain (AL) amyloidosis with an ultra-high level of serum free light-chain (FLC) .Methods:Five hundred and ninety-five patients with AL amyloidosis were retrospectively reviewed between January 2009 and January 2020 at Peking Union Medical College Hospital. We analyzed the clinical features and prognosis of patients with ultra-high FLC levels [difference between involved and uninvolved light chains (dFLC) >500 mg/L; n=124] and those without ultra-high FLC levels (dFLC≤500 mg/L; n=471) . Results:Patients with ultra-high FLC presented with more frequent cardiac involvement (82.3% vs 70.1%, P=0.007) , and a higher percentage of patients with 2004 Mayo Ⅲ stage (41.8% vs 33.8%, P=0.029) , but less frequent renal involvement than patients without an ultra-high FLC (59.7% vs 71.8%, P=0.009) . Patients with an ultra-high FLC achieved a lower proportion of hematologic (72.4% vs 82.3%, P=0.048) and cardiac response (37.3% vs 54.7%, P=0.016) and had shorter overall survival (13.0 months vs not reached, P<0.001) and a higher early death rate within 3 months (28.2% vs 11.3%, P<0.001) than those without an ultra-high FLC. Ultra-high FLC independently predicted worse prognosis in patients with AL amyloidosis ( HR=2.279, 95% CI 1.685-3.083, P<0.001) . Conclusions:Patients with an initially ultra-high FLC represented a subgroup with more common cardiac involvement, more advanced cardiac stages, and extremely poor prognosis.

Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Retrospective Studies ; Stomach Neoplasms/surgery*