Antibody-drug conjugates (ADCs) are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker. Currently, 15 ADCs have been clinically approved worldwide. More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs. ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development. It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells, thereby producing promising antitumor efficacy and favorable adverse effect profiles. However, emergence of drug resistance has severely hindered the clinical efficacy of ADCs. In this review, we introduce the structure and mechanism of ADCs, describe the development of ADCs, summarized the latest research about the mechanisms of ADC resistance, discussed the strategies to overcome ADCs resistance, and predicted biomarkers for treatment response to ADC, aiming to contribute to the development of ADCs in the future.

Objective:To investigate the impact of rosacea on patients＇ quality of life and mental health, and to analyze variations across different subtypes, gender, sun exposure, smoking status, ethnicity, and educational levels, as well as patients＇ demands for treatment.Methods:It was a cross-sectional study from October 2022 to January 2024, 177 rosacea patients from the Department of Dermatology, the First Affiliated Hospital of Kunming Medical University were surveyed. The cohort comprised 36 males and 141 females, with a median age of 35 (29, 44) years. Data collected through questionnaires included general information, Dermatology Life Quality Index (DLQI), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Patient Need Questionnaire (PNQ). Statistical analysis was conducted on the collected data.Results:The median DLQI score was 10 (3, 15), indicating moderate impact. The median GAD-7 score was 5 (2, 7), suggesting mild anxiety; while the median PHQ-9 score was 6 (2, 9), indicating mild depression. Female patients scored higher in both DLQI and GAD-7 than males ( P<0.05). Papulopustular subtypes had higher DLQI and GAD-7 scores compared to other subtypes ( P<0.01). Patients with lower education levels scored higher in DLQI and GAD-7 than those with higher education ( P<0.01), and non-smokers had higher GAD-7 scores than smokers ( P<0.05). Significant positive correlations were found between DLQI and PHQ-9 ( r=0.39, P<0.01), and DLQI and GAD-7 ( r=0.51, P<0.01), as well as between PHQ-9 and GAD-7 ( r=0.59, P<0.01). Regarding treatment needs, 159 patients (89.8%) expressed a strong desire for a clear diagnosis and treatment plan, and the same number wished for a complete resolution of all skin lesions. Female patients consistently demonstrated significantly stronger demands in all 28 treatment need items (all P<0.05). Conclusions:Rosacea significantly affects patients＇ quality of life and mental health, particularly among females, individuals with papulopustular subtypes, and those with lower education levels. There is a strong demand for definitive diagnostic and therapeutic plans, especially among female patients.

Amyloidosis is a metabolic disease characterized by the deposition of amyloidogenic fibrils in multiple organs, which causes structural disorders, leading to a decline in organ function and in the case of myocardial involvement, damage to the structure and function of the heart, which is the main cause of mortality. However, the disease is often misdiagnosed or underdiagnosed due to its insidious onset and lack of specificity in clinical manifestations. 99Tc m-pyrophosphate (PYP) SPECT is a noninvasive test that can not only identify cardiac amyloid deposits at an early stage but also provide a useful tool for the diagnosis of cardiac amyloidosis. This article briefly describes the traditional screening methods for cardiac amyloidosis, outlines their limitations, and focuses on the clinical diagnostic value of 99Tc m-PYP SPECT in cardiac amyloidosis.

Objective To explore the correlation between HbA1c level and carotid plaque stability in type 2 diabetes mellitus(T2DM)patients.Methods From October 2018 to October 2020,100 T2DM patients who visited our hospital and underwent carotid artery ultrasound examination with a plaque thickness greater than 1.5 mm were included in this study.According to HbA1c levels,they were divided into HbA1c≤7%group(n=21),7%9%group(n=51).Results The FPGs of the 7%9%groups were higher than that of the HbA1c≤7%group(P<0.01).The plaque thickness gradually increased from group HbA1c≤7%,7%9%groups(P<0.01),and the proportion of high-level enhancement in the overall,proximal,middle,and distal segments of the plaque increased in sequence(P<0.05 or P<0.01).Pearson correlation analysis showed that HbA1c,FPG,and 2 hPG were positively correlated with plaque thickness and length(P<0.05).Spearman correlation analysis showed that HbA1c was positively correlated with the smoothness of the plaque surface,the presence of extremely low echogenicity within the plaque,and the overall,proximal,central,and distal enhancement intensity of the plaque(P<0.05).Conclusion HbA1c can not only evaluate the blood glucose control of T2DM patients,but also has a certain correlation with the stability of carotid plaque,with a trend of poorer plaque stability as HbA1c increases.

ObjectiveTo compare the effects of topical application of Modified Sanhuang Powder （加味三黄散， MSP） combined with cold compression versus cold compression alone on swelling and pain after knee arthroscopy through a retrospective cohort study. MethodsMedical records of 134 patients with knee arthroscopy-induced knee swelling and pain were divided into non-exposure group （51 cases） and exposure group （83 cases） based on whether they used MSP for external application after surgery. The non-exposure group received simple cold compression therapy in addition to functional exercise and routine treatment after surgery， while the exposure group received topical MSP on the basis of what were given in the non-exposure group. The Visual Analog Scale （VAS） scores were compared between the two groups before and 7 days after treatment， and knee swelling measurements were taken before and 3， 5， and 7 days after treatment. The clinical effective rate was compared between the two groups. ResultsThe VAS scores in both groups were lower after treatment （P＜0.05）， and the exposure group had lower scores than the non-exposure group （P＜0.05）. On the 3rd， 5th， and 7th days of treatment， the scores on swelling at 2 cm above the superior pole of the patella， at the midline of the patella， and 5 cm below the inferior pole of the patella significantly decreased after treatment in both groups （P＜0.05）， and the exposure group had lower scores than the non-exposure group （P＜0.05）. The total clinical effective rate in the exposure group was 91.56% （76/83）， which was higher than 78.43% （40/51） in the non-exposure group （P＜0.05）. ConclusionTopical application of MSP combined with cold compression is effective in relieving postoperative swelling and pain after knee arthroscopy and is superior to cold compress alone.

OBJECTIVE：To study the relationship of polymorphism of clopidogrel absorption and metabolism related genes CYP2C19（* 2，* 3，* 17），ABCB1 C3435T and PON1 Q192R in patients with coronary heart disease in Xinjiang Uygur Autonomous Region ，and to explore the characteristics of population and combined diseases. METHODS ：A total of 1 126 patients with coronary heart disease who underwent clopidogrel absorption and metabolism related gene testing during hospitalization in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to June 2020 were included as the study subjects. The gender，age，body mass index （BMI），nationality and the proportion of combined with hypertension and diabetes were compared among different CYP2C19 metabolic phenotypes and ABCB1 C3435T and PON1 Q192R genotypes. RESULTS ：Among 1 126 patients，1 126 had CYP2C19 * 2，* 3 and * 17 genotypes，1 109 had ABCB1 C3435T genotype and 1 123 had PON1 Q192R genotype. The distribution of each genotype was in line with Hardy-Weinberg balance （P＞0.05）. There were 66（5.86％）， com 459（40.76％），476（42.27％） and 125（11.10％）patients with CYP2C19 ultra-rapid metabolizer （UM）， extensive metabolizer（EM），intermediate metabolizer （IM）and poor metabolizer（PM），respectively. The proportion of patients with UM metabolism phenotype with BMI ＞24 was significantly higher than those of patients with IM and PM metabolism phenotypes （P＜0.05）. The proportion of Han nationality patients with UM metabolic phenotype was significantly lower than those of patients with EM ，IM and PM metabolic phenotypes （P＜0.05）；the proportion of Uygur nationality was significantly higher than that of patients with EM ，IM and PM metabolic phenotypes （P＜ 0.05）. There were 355，538 and 216 patients with ABCB1 C3435T wild-type（CC），heterozygous（CT）and mutant homozygous （TT）genotypes，respectively；the proportion of Han nationality in TT genotype patients was significantly lower than that in CC and CT genotype patients （P＜0.05），and the proportion of Uygur nationality was significantly higher than that in CC and CT genotype patients （P＜0.05）；the proportion of TT genotype patients with diabetes was significantly higher than that of patients with CT genotype （P＜0.05）. There were 365，519 and 239 patients with PON1 Q192R wild-type（GG），heterozygous（GA）and mutant homozygous （AA），respectively；the proportion of Han nationality in AA genotype patients was significantly lower than that in GG and GA genotype patients （P＜0.05），and the proportion of Uygur nationality was significantly higher than that of GG and GA genotype patients （P＜0.05）；the proportion of Han nationality and BMI ≤24 in patients with AA genotype were significantly lower than those with GA genotype （P＜0.05），and the proportion of Uygur nationality ，BMI＞24 and hypertension were significantly higher than those in GA genotype patients （P＜0.05）. CONCLUSIONS ：There are significant nationality differences among patients with different CYP2C19 metabolic phenotypes and ABCB1 C3435T and PON1 Q192R genotypes. In addition，patients with BMI ＞24 account for high proportion among CYP2C19 UM metabolism genotype ；patients with diabetes account for high proportion among ABCB1 C3435T TT genotype ；patients with BMI ＞24 and hypertension account for high proportion among PON1 Q192R AA genotype.

Objective:To evaluate the effects of vaccine switch on the levels of neutralizing antibody (NA) of poliovirus in children aged<12 years.Methods:Subjects aged<12 years from 9 districts in Fujian province were chosen by stratified cluster and complete random sampling method. Blood samples were collected for testing NA of poliovirus by microcell neutralization.Results:A total of 2 134 subjects aged<12 years were selected. The positive rate of NA against PVⅠand Ⅲ were 98.64% and 95.83%; and geometric mean titers (GMTs) were 1∶259.35 and 1∶105.14, respectively. The GMTs presented a trend of decreasing as age increased. Compared to trivalent oral poliovirus vaccine (tOPV), bivalent oral poliovirus vaccine (bOPV) and inactivated poliovirus vaccine (IPV) induced higher GMTs of NA against poliovirusⅠand Ⅲ respectively. Among 182 children aged<5 years, the positive rate of NA against PVⅠ, Ⅱ, Ⅲ were 97.25%, 76.37% and 92.86%. There were statistical differences among the three types ( χ2=44.44, P=0.000). The rate of NA against PVⅡwas significantly lower than those ofⅠand Ⅲ (Ⅱ vs. I: χ2=34.65, P=0.000; Ⅱ vs. Ⅲ: χ2=18.99, P=0.000). And the GMTs of NA against PV Ⅰ, Ⅱ, Ⅲ were 1∶368.96、1∶23.06 and 1∶183.10, which were significantly different ( F=156.54, P=0.000). The GMT of PVⅠwas the highest, PV Ⅲ was the second, PVⅡ was lowest (pairwise comparison showed values of P all were 0.000). The analysis of general linear model showed that the interval between the date of last immunization and the date of sample collection would affect the GMTs of PVⅠand Ⅲ, different vaccine models would affect only the GMT of PV Ⅰ. The age maybe was a confounding factor. But no factors would affect the GMT of PV Ⅱ. Conclusions:After the vaccine switch, the level of NA against PVⅠand PV Ⅲ were still maintaining high level, but the level of PVⅡamong children<5 years was at relatively low level, which indicated that the surveillance should be strengthened.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective To evaluate the inactivation effect of heat inactivation and three common chemical disinfectants on enterovirus group A 71 (EV-A71),provide basic data for disinfection work after laboratory activities in enterovirus secondary biosafety laboratory.Methods EV-A71 virus was treated at different temperatures and different disinfectant concentrations according to different time.The inactivated virus was inoculated into 96-well cell culture plates,and the cytopathic effect was observed and recorded.Finally,the virus titer of the virus treatment solution was calculated.Results After inactivation at 56 ℃ for 30 min,the inactivation logarithm of EV-A71 was more than 6,and inactivation at 65 ℃ for 30 rin,70 ℃ for 10 min,no infection was observed.Three chemical disinfectants could effectively inactivate a certain titer of EV-A71 at a certain concentration and treatment time.Conclusions The inactivation effect of EV-A71 virus is related to factors such as thermal inactivation temperature,chemical disinfectant concentration,and treatment time.Studying the inactivation curve of EV-A71 is beneficial to the selection of inactivation conditions in different inactivation environments.

Objective: To evaluate 2017 poliovirus surveillance in Qinghai Province. Methods: According to the World Health Organization (WHO) 4 th edition of the polio laboratory manual procedure for virus isolation, the isolated L20B positive strain was identified as intratypic differentiation (ITD) by the China Center for Disease Control and Prevention, CDC). The National Polio Laboratory performed the nucleotide sequence determination of the capsid protein VP1 coding region of poliovirus (PV) and analyzed the poliovirus surveillance and the result of analysis of the cases with acute flaccid paralysis (AFP) reported in Qinghai Province in 2017 and stool samples of healthy children. Results: In 2017, Qinghai CDC Polio Laboratory received specimens of 211 AFP cases and healthy stool samples. PV2 strains were isolated with a separation rate of 0.95%. Non-polio enterovirus (NPEV) strains were isolated from 25 strains with the isolation rate of 11.85%. Two PVs were used for ITD. All of them were vaccine-associated strains. Conclusions In 2017, the Qinghai CDC Polio Laboratory did not find any poliovirus and vaccine-derived poliovirus in the AFP cases and stool samples from healthy persons, maintaining the polio-free status.