Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant

Objective To evaluate the effectiveness of the integrated schistosomiasis control measures in Changzhou City from 2015 to 2020, so as to provide insights into the formulation of the strategy used to consolidate the schistosomiasis elimination achievements. Methods The annual schistosomiasis control working report and integrated schistosomiasis control data were collected in Changzhou City from 2015 to 2020, and the prevalence of Schistosoma japonicum infections in humans and livestock and snail status were analyzed to evaluate the effectiveness of the integrated schistosomiasis control measures. Results During the period from 2015 to 2020, a total of 112 061 person-time individuals received serological tests for S. japonicum infections in Changzhou City, and the sero-prevalence was 0.15% to 1.09% during the 6-year period, with a significant difference seen among years (χ² = 288.11, P < 0.05). From 2015 to 2020, a total of 13 435 person-time individuals received stool examinations, with no egg-positives identified; among 5 840 herd-time livestock receiving schistosomiasis examinations, no positives were detected, while a 100% coverage of fencing livestock was seen each year. During the 6-year period, a total of 38.40 hm² snail habitats were found, including 8.97 hm² emerging snail habitats, and among the 2 344 snails dissected, no S. japonicum infection was found. Chemical treatment covered an area of 385.71 hm², and environmental improvements covered an area of 200.39 hm². The mean density of living snails was less than 0.1 snails/0.1 m² in snail habitats found in Changzhou City each year from 2015 to 2020, and the coverage of harmless toilets was 100% in 2020. During the 6-year period, a total of 3.740 6 million person-time individuals were given schistosomiasis health education in Changzhou City. Conclusions Changzhou City is now at the post-elimination surveillance stage; however, there are still factors affecting schistosomiasis transmission. The schistosomiasis surveillance system remains to be improved to consolidate the schistosomiasis elimination achievements in Changzhou City.

Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Five alkaloids were isolated from a decoction of Uncaria rhynchophylla by a combination of various chromatographic techniques, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and reversed phase HPLC. Their structures were characterized by comprehensive analyses of spectroscopic data as monoterpene indole alkaloids (+)-(7R)-3-oxo-7-hydroxy-3,7-seco-dihydrorhynchohylline (1), (+)-(7S)-3-oxo-7-hydroxy-3,7-seco-dihydrorhyncho-hylline (2), (+)-(7R)-3-oxo-7-hydroxy-3,7-seco-rhynchohylline (3) and (+)-(7S)-3-oxo-7-hydroxy-3,7-seco-rhynchohylline (4), and a β-carboline alkaloid 1,2,3,4-tetrahydro-1-oxo-β-carboline (5). Among them, 1 and 2 are new compounds, 3 and 4 are new natural products that were semi-synthesized from isorhynchohylline with incorrect specific rotations, and 5 is isolated for the first time from the genus Uncaria.

Objective To assess the state of schistosomiasis elimination in 6 districts of Changzhou City, Jiangsu Province, so as to provide the evidence for the formulation of consolidation measures. Methods Three towns (streets) were selected according to the schistosomiasis epidemic degree in each district, and one village was sampled from each town. The on-site assessment was carried out between 2016 and 2017, including Oncomelania hupensis snail survey, population investigation and domestic animal investigation. In addition, the related data and materials were evaluated and the monitoring ability was assessed. Results In the history, there were 54 endemic towns, 368 endemic villages in Changzhou City, with a total area of 3 934.79 hm² of historic snail spots, and 114 990 schistosomiasis cases so far. In the field assessment in 6 districts, a total of 26 environments were surveyed, with the surveyed area of 36.23 hm², and there were no living snails captured in each village. A total of 18 199 people were examined for schistosome infection, 255 were blood test positive, and the sero-positive rate was 1.40%. The stool examination was done in 255 sero-positive cases, and no cases were stool-positive. A total of 779 domestic animals were investigated, including 200 cattle, 179 sheep and 400 pigs, and no infections were detected. The files regarding the snail status and schistosomiasis epidemic situation, and the monitoring data were complete and accurate in 6 districts. The annual investment funds for schistosomiasis prevention were 3 120 000 Yuan in Changzhou City, and the number of staff working for schistosomiasis prevention was 86 totally, which could meet the requirements of high quality monitoring. Conclusions All 6 districts of Changzhou City have met the requirements of schistosomiasis elimination.

Aim To investigate the effects of gastrodin on SH-SY5Y cell autophagy induced by methamphet-amine (METH) and the underlying mechanisms. Methods SY5Y cells were treated by METH with the concentration of 0.5,1.0,1.5,2.0,2.5,3.0 mmol·L-1for 24 h. The morphological changes were ob-served by microscopy,the expression of LC3-Ⅱ,Bec-lin-1,Akt,p-Akt,mTOR and p-mTOR were detected by Western blot. Gastrodin was added to the medium 1 h before METH treatment. Results The SY 5 Y cells were morphologically featured by shrinkage and den-drite disruption after exposed to METH(0~3 mmol· L-1),and autophagic vacuoles occurred in cytoplasm. The expression of LC3-Ⅱ increased over METH dose. Confocal results showed that LC3-Ⅱsignificantly in-creased in METH group as compared with control, while decreased in METH+ Gastrodin group. The ex-pression levels of LC3-Ⅱand Beclin-1 significantly in-creased (P<0.01) in METH group, p-mTOR and p-Akt decreased, and mTOR and Akt showed no signifi-cant difference as compared with control. However, the gastrodin could decrease the expression of LC3-Ⅱand Beclin-1 and increase the expression of mTOR,p-mTOR,Akt and p-Akt as compared with METH-trea-ted groups. Conclusions METH can induce SY5Y cells autophagy. The protective effect of gastrodin a-gainst METH-induced autophag may be related to gast-rodin regulation mTOR and Akt signaling pathway.

Objective To observe the curative mechanism and effect of neurotoxicity injury induced by methamphetamine (MA) and the neuroprotective effects of gastrodin interfered. Whether the expression of astrocyte and proinflammatory cytokines has contributed to the effects of gastrodin.Methods 48 healthy male SD rats were randomly divided into three groups: control group (Daily intraperitoneal injection of saline for 8 weeks),MA group (A dose of 10 mg/kg MA was administered every day for four weeks,then given daily intraperitoneal injection with 10 mg/kg saline for 4 weeks) and gastrodin group (A dose of 10 mg/kg MA was administered every day for four weeks,then given daily intraperitoneal injection with 10 mg/kg gastrodin for 4weeks) . The behavioral changes of rats were measured by conditioned place preference ( CPP) and sterotyped behavior ( SB) induced by methamphetamine. Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein (GFAP) and NEUN in rat frontal cortex.The expression of IL－6 and TNF－α were detected by quantity RT－PCR and westrn bloting.Results Compa MA depndent 4 weeks group with control group, the scores of sterotyped behavior of MA depndent groups had signficantly increased (P＜0.01) . Comparing MA depndent 4 weeks group with MA depndent 4 weeks+gastrodin group, the scores of sterotyped behavior of MA dependent 4 weeks group had obviously decreaseed (P＜0.01) . Compared with the control group, the expression of GFAP of MA dependent 4 weeks group decreased and the expression of NEUN increased. Compared MA dependent 4 weeks group with control group, the expression of IL－ 6 and TNF－α increased (P＜0.01) . Compared MA dependent 4 weeks+gastrodian group with MA dependent 4 weeks group, the expression of TNF－α and IL－6 significantly reduced (P＜0.01) . Conclusion The neurological damage induced by methamphetamine might be related to the activation of astrocytes and the high expression of inflammatory cytokines including IL－6 and TNF－α. Gastrodin could abate the neurological injury of methamphetamine dependence via reducing the activation of astrocytes and decreasing the expression of IL－6 and TNF－α.

Sixteen lignanoids were isolated from an aqueous extract of the commonly used Chinese traditional medicine Dangshen, the dried roots of Codonopsis pilosula, by using a combination of various chromatographic techniques, including silica gel, macroporous adsorbent resin, MCI resin, sephadex LH-20, and reversed phase semi-preparative HPLC. On the basis of spectral data analysis, their structures were elucidated and identified as (-)-(7R, 7'R, 8R, 8'S)-4, 4'-dihydroxy-3, 3', 5, 5', 7-pentamethoxy-2, 7'-cyclolignane (1), (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranosyl-(1"'→2")-β-D-glucopyranoside (2), (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol (3), (+)-(7S, 8R)-dehydrodiconiferyl alcohol (4), (+)-balanophonin (5), (+)-demethoxypinoresinol (6), (+)-pinoresinol (7), (+)-epipinoresinol (8), (-)-syringaresinol (9), (-)-medioresinol (10), (-)-lariciresinol (11), (-)-secoisolariciresinol (12), (-)-ent-isolariciresinol (13), (+)-(7S, 8S)-3-methoxy-3', 7-expoxy-8, 4'-neolignan-4, 9, 9'-triol (14), (+)-(7S, 8R)-3', 4-dihydroxy-3-methoxy-8, 4'-neolignan (15), and (-)-(7R, 8R)-3', 4-dihydroxy-3-methoxy-8, 4'-neolignan (16). All these compounds were isolated from C. pilosula for the first time, while compound 1 is a new natural product of 2, 7'-cyclolignan and 2 is a new 4', 7-epoxy-8, 3'-neolignan diglucoside. Compound 12 showed activity against Fe²⁺-cysteine induced rat liver microsomal lipid peroxidation with an inhibition ratio of (63.4±8.3)% at 1×10^-5 mol·L^-1.