Since the approval of gemtuzumab ozogamicin,an antibody-drug conjugate(ADC)targeting CD33 in 2000,13 ADC drugs have been approved by the FDA.Although these drugs have clearly improved the survival of patients with various types of advanced cancers,their significant toxicity has compromised their therapeutic benefits.The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities,where the payload drug is a determining factor.Antibody and linker may also affect the degree of toxicity.Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency,but treatment-related adverse reactions also increase accordingly.This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies,including but not limited to optimizing linker molecules,upgrading antibody design,and changing drug administration strategies,to improve the overall safety profile of ADC drugs.

ObjectiveTo explore the effect of home exercise on pain, function and quality of life after operation for rotator cuff injury. MethodsFrom June, 2023 to June, 2024, 45 patients after operation for rotator cuff injury were selected from Xuzhou Rehabilitation Hospital Affiliated to Xuzhou Medical University and Xuzhou Central Hospital, and randomly divided into conventional group (n = 15), home-based group (n = 15) and combined group (n = 15). The conventional group received an eight-week routine rehabilitation program in hospital, the home-based group received an eight-week home exercise prescription training, and the combined group first received four weeks of routine rehabilitation in hospital, and followed by four weeks of home exercise prescription training. They were assessed with Visual Analogue Scale for pain (VAS), University of California at Los Angeles shoulder rating scale (UCLA), Constant-Murley Score (CMS), range of motion (ROM) of shoulder, and the Short-form of Health Survey-36 (SF-36) before treatment, and four and eight weeks after treatment. ResultsVAS scores decreased in all the three groups four and eight weeks after treatment (Z > 2.964, P < 0.001), which was the most in the home-based group four weeks after treatment (|Z| > 2.531, P < 0.05). The main effect of time was significant in scores of UCLA, CMS, and physical health and mental health of SF-36 (F > 498.102, P < 0.001), which improved after treatment (P < 0.001). The main effect of group was significant in score of mental health of SF-36 (F = 7.408, P = 0.002), which was the most in the home-based group four and eight weeks after treatment (P < 0.01). The interaction was significant in score of physical health of SF-36 (F = 10.138, P < 0.001), which was the least in the home-based group four weeks after treatment (P < 0.05). The main effect of time was significant in every direction of ROM, which improved after treatment (P < 0.001). The interaction was significant in ROM of abduction and external rotation (F > 4.059, P < 0.01), and almost significant in ROM of flexion (F = 2.412, P = 0.055). However, ROM of flexion was less in the home-based group than in the combined group four weeks after treatment (P = 0.047), which was less in the home-based group than in the conventional group eight weeks after treatment (P = 0.042); ROM of abduction was the least in the home-based group four weeks after treatment (P < 0.01), which was less in the home-based group than in the combined group eight weeks after treatment (P = 0.046); ROM of external rotation was less in the home-based group than in the combined group four weeks after treatment (P = 0.022). ConclusionHome exercise is effective on pain, function and quality of life in patients after operation for rotator cuff injury. There are benefits with both home exercise and institution-based rehabilitation, and almost the same in a whole eight weeks after treatment.

ObjectiveTo explore the effect and mechanism of Sishenwan-containing serum on aerobic glycolysis in human colon cancer HCT116 cells. MethodCell counting kit-8 （CCK-8） was used to detect the cell viability of colon cancer HCT116 cells after treatment with Sishenwan-containing serum （2.5%， 5%， and 10%） for 24， 48， 72 h. The concentration of lactic acid， the content of intracellular glucose， and the activity of hexokinase （HK） and fructose-6-phosphate kinase （PFK） in the cell culture medium were detected by the micro-method. The content of glucose transporter 1 （GluT1） mRNA was detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of GluT1 and methyltransferase-like 3 （MettL3） was detected by Western blot. The expression of GluT1 in cells was detected by immunofluorescence and the level of N6-methyladenosine （m⁶A） RNA methylation was detected by colorimetry. ResultCompared with the normal serum， 2.5%， 5%， and 10% Sishenwan-containing serum had no significant effect on the viability of HCT116 cells at 24 h， while 10% Sishenwan-containing serum showed a significant inhibitory effect on the viability of HCT116 cells at 48 h （P<0.05）. Hence， 10% Sishenwan-containing serum was used in subsequent experiments， and the intervention time was 48 h. Compared with the normal serum， 10% Sishenwan-containing serum could reduce lactate production （P<0.05）， down-regulate glucose uptake （P<0.05）， and blunt the activities of HK and PFK， the key rate-limiting enzymes of glycolysis （P<0.05）. Meanwhile， 10% Sishenwan-containing serum could decrease the expression of GluT1 protein （P<0.01） and mRNA （P<0.05） and reduce the proportion of cells expressing GluT1 （P<0.01）. Compared with the normal serum， Sishenwan-containing serum also decreased the protein content of MettL3 （P<0.05） and the methylation level of m⁶A RNA （P<0.01）. ConclusionSishenwan can inhibit glycolysis in colon cancer cells， and its inhibitory mechanism may be related to reducing MettL3 overexpression， inhibiting m⁶A RNA methylation， and down-regulating GluT1 and the activities of intracellular aerobic glycolysis-related enzymes such as HK and PFK.

Except for IgA nephropathy, membranous nephropathy (MN) is the most common primary glomerulonephritis in China. Neural epidermal growth factor-like 1 protein (NELL-1) has been currently considered as one of the target antigens for diagnosis of primary MN. Moyamoya syndrome is a syndrome with clinical and imaging manifestations of moyamoya disease and possible vascular stenosis. By far, primary MN complicated with moyamoya syndrome has not been reported internationally. The paper reports a case of NELL-1-related MN complicated with moyamoya syndrome and reviews relevant literature to provide evidence for clinical diagnosis and treatment.

Females increase aggression for mating opportunities and for acquiring reproductive resources. Although the close relationship between female aggression and mating status is widely appreciated, whether and how female aggression is regulated by mating-related cues remains poorly understood. Here we report an interesting observation that Drosophila virgin females initiate high-frequency attacks toward mated females. We identify 11-cis-vaccenyl acetate (cVA), a male-derived pheromone transferred to females during mating, which promotes virgin female aggression. We subsequently reveal a cVA-responsive neural circuit consisting of four orders of neurons, including Or67d, DA1, aSP-g, and pC1 neurons, that mediate cVA-induced virgin female aggression. We also determine that aSP-g neurons release acetylcholine (ACh) to excite pC1 neurons via the nicotinic ACh receptor nAChRα7. Together, beyond revealing cVA as a mating-related inducer of virgin female aggression, our results identify a neural circuit linking the chemosensory perception of mating-related cues to aggressive behavior in Drosophila females.
Animals ; Male ; Female ; Drosophila/physiology* ; Drosophila Proteins/physiology* ; Cues ; Sexual Behavior, Animal/physiology* ; Aggression/physiology* ; Drosophila melanogaster/physiology*

Animals ; Aedes/physiology* ; Hot Temperature ; Feeding Behavior ; Behavior, Animal/physiology*

The choice of females to accept or reject male courtship is a critical decision for animal reproduction. Serotonin (5-hydroxytryptamine; 5-HT) has been found to regulate sexual behavior in many species, but it is unclear how 5-HT and its receptors function to regulate different aspects of sexual behavior. Here we used Drosophila melanogaster as the model animal to investigate how 5-HT and its receptors modulate female sexual receptivity. We found that knockout of tryptophan hydroxylase (Trh), which is involved in the biosynthesis of 5-HT, severely reduced virgin female receptivity without affecting post-mating behaviors. We identified a subset of sexually dimorphic Trh neurons that co-expressed fruitless (fru), in which the activity was correlated with sexual receptivity in females. We also found that 5-HT_1A and 5-HT₇ receptors regulate virgin female receptivity. Our findings demonstrate how 5-HT functions in sexually dimorphic neurons to promote virgin female receptivity through two of its receptors.
Animals ; Male ; Female ; Drosophila/physiology* ; Drosophila melanogaster/physiology* ; Serotonin ; Drosophila Proteins/physiology* ; Sexual Behavior, Animal/physiology* ; Transcription Factors ; Nerve Tissue Proteins

Objective:To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer.Methods:This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants′ characteristics and screening results of the two groups were compared by χ 2 test, Fisher exact test or Wilcoxon rank-sum test. Results:A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ2=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ2=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ2=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ2=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ2=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ2=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ2=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ2=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ2=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ2=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ2=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ2=0.082, P=0.774). Conclusions:Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

Objective:To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer.Methods:This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants′ characteristics and screening results of the two groups were compared by χ 2 test, Fisher exact test or Wilcoxon rank-sum test. Results:A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ2=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ2=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ2=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ2=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ2=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ2=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ2=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ2=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ2=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ2=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ2=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ2=0.082, P=0.774). Conclusions:Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

Objective:To explore the effects of dietary glycemic load (GL) during first trimester on the risk of gestational diabetes mellitus (GDM).Methods:A prospective study was conducted among healthy women with singleton pregnancy at 8-14 weeks of gestation in a maternity out-patient clinic of maternal-and-child health care institution in Chengdu, Sichuan province. Information on dietary intake during the first trimester was collected through a 3-day 24-hour dietary recall. Glycemic index (GI) values were obtained from China Food Composition Tables (Standard Edition) and International Tables of Glycemic Index and Glycemic Load Values (2008). Dietary GL and GLs of staple foods were calculated based on GI values and the amount of carbohydrate consumed per day. Diagnostic criteria of GDM was followed the Guidelines for Diagnosis and Treatment of Pregnancy Diabetes in China (2014), and used on participants who underwent an oral glucose tolerant test during 24-28 weeks of gestation. Log-binomial regression models were used to explore the associations between both quartiles of dietary GL, GLs of staple foods and the risks of GDM,respectively.Results:The medians of dietary GL and GL of staple foods were 145.70 (113.23-180.85) and 121.05 (89.08-155.70), respectively. The median GL of both rice and tubers were 73.14 (43.89-107.50) and 3.43 (0.00-9.84), respectively. After adjusting for the age at pregnancy, pre-pregnancy body mass index and other confounding factors, results of log-binomial regressions analysis showed that when compared with the lowest quartile of dietary GL group, the third and highest quartiles of dietary GL groups increased the risk of GDM ( RR=1.47, 95% CI: 1.20-1.80; RR=1.31, 95% CI: 1.04-1.64), respectively. Compared with the lowest quartile of GL of staple foods, the third and highest quartiles of GL of staple foods groups also increased the risk of GDM ( RR=1.28, 95% CI: 1.04-1.58; RR=1.27, 95% CI: 1.02-1.60), respectively. The third and highest quartiles of GL of rice groups increased the risk of GDM ( RR=1.30, 95% CI: 1.06-1.59; RR=1.28, 95% CI: 1.03-1.59), respectively, than the lowest quartile of GL of rice group. When compared with the lowest quartile of GL of tubers group, the highest quartile of GL of tubers group increased the risk of GDM ( RR=1.30, 95% CI: 1.09-1.54). However, we did not notice the effects of wheat GL and coarse grain GL on the risk of GDM. Conclusions:A positive association was found between dietary glycemic load and the risk of GDM. Higher dietary glycemic load, especially in rice and tubers during first trimester, seemed to have increased the risk of GDM.