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 explore the clinical efficacy of the first dorsal metatarsal artery pedicled lateral toe bilobed flap in repairing the finger pulp defects of two adjacent fingers.Methods:This study was a retrospective observational study. From January 2018 to December 2022, 9 patients with finger pulp defects in two adjacent fingers who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 6 males and 3 females, aged 26 to 48 years. The injured fingers were the index finger and middle finger (5 cases) or the middle finger and ring finger (4 cases). After debridement, the wound area of a single finger ranged from 1.2 cm×0.8 cm to 3.2 cm×2.8 cm. The finger pulp defects of two adjacent fingers were repaired with the first dorsal metatarsal artery pedicled lateral toe bilobed flap, and the two adjacent fingers were sutured together. The area of single flap ranged from 1.5 cm×1.0 cm to 3.5 cm×3.0 cm. The wound in the flap donor site was sutured directly or repaired with full-thickness skin graft from the groin region. The finger separation surgery was performed 3 weeks after surgery. The survival and blood supply of flaps, and survival of skin grafts and wound healing of the donor sites were observed after surgery. During follow-up, the texture, sliding, and shape of the flap, movement function of the finger, and the shape and function of the foot donor site were observed. At the last follow-up, the sensory of the flap was evaluated according to the sensory evaluation standard of the British Medical Research Council, and the hand function was evaluated according to the functional evaluation trial standard for severed finger replantation of the Hand Surgery Society of the Chinese Medical Association. Results:After surgery, all the flaps of 9 patients survived without vascular crisis. The flaps were soft in texture and good in shape. One patient had partial necrosis at the edge of the skin graft in the toe, and the wound healed after dressing change; the skin grafts in the toe in the other 8 patients survived, and the wounds healed well. During follow-up of 12 to 18 months after surgery, the flaps had soft texture, good elasticity, low sliding, and good shape. The finger movement function was normal. The wound in foot donor site recovered well without ulceration and deformity, and walking was not affected. At the last follow-up, the sensation of the flaps was sensitive, of which 8 flaps reached S3 and 10 flaps reached S3 + in sensation, and the two-point discrimination distance of the flaps was 9-13 mm. The functional scores of the affected fingers were 85 to 95, all of which were excellent. Conclusions:The first dorsal metatarsal artery pedicled lateral toe bilobed flap can repair finger pulp defects of two adjacent fingers at the same time, and the appearance, sensation, and function of the affected fingers recovered well after surgery, with less damage to the foot donor site. It is one of good methods to repair finger pulp defects of two adjacent fingers in clinic.

Objective:To explore the clinical efficacy of anterolateral thigh perforator flap (ALTPF) in treatment of extensive wound of Degree IV burns in limbs.Methods:A retrospective analysis was conducted on 9 patients who had extensive wound of Degree IV burns in limbs caused by stove burns admitted to Department of Burns and Plastic Surgery, the 988th Hospital of the Joint Logistics Support Force of the Chinese PLA between January 2017 and January 2024. Among the patients, there were 8 males and 1 female, aged between 36 and 63 years. Three patients had the wound from anterior leg to dorsal foot, 3 from leg down to ankle, 1 from forearm to hand and 2 from arm to forearm. Area of burns ranged from 20 cm × 15 cm to 30 cm × 25 cm, and all patients were treated by free ALTPF. According to whether the main artery at the recipient site was feasible for direct anastomosis with the vessels carried in flap, 4 patients were treated by bilateral parallel ALTPFs, and 5 were treated by unilateral ultra-long internally supercharged ALTPF. A total of 13 ALTPFs were harvested, with individual flap size at 20 cm × 8 cm to 46 cm × 12 cm. Donor sites were directly sutured. Time for flap harvesting, flap survival and wound healing time were records. Scheduled postoperative follow-up was conducted at outpatient clinic and via telephone interviews to evaluate functional recovery. Follow-up assessments included evaluation of flap condition, two-point discrimination (TPD), recovery of joint function at recipient sites, flap appearance and donor site recovery.Results:The time for flap harvest was 1.0 to 4.5 hours. All 13 ALTPFs successfully survived. The time from surgery to healing of recipient sites was 18 to 72 days, and all donor sites healed. Over the postoperative follow-up that lasted for 6 to 34 months, the recipient sites had found with good cosmetic outcomes, without osteomyelitis or deep tissue infection. Four ALTPFs in 2 patients were found swelling, which were revised at 6 months after surgery. Four ALTPFs in other 2 patients had pigment deposition at edges. One ALTPF was scalded, which healed after dressing changes but left with patchy scars. The remaining ALTPFs were soft, elastic, free from pain and well-perfused, with regained protective sensation at S 3. However, all of the ALTPFs failed to detect TPD. Six patients with lower limb injuries were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) ankle hindfoot scoring system: 2 patients were rated as excellent and 4 were rated as good. Three patients with upper limb injuries were evaluated using Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association: 1 patient was rated as excellent and 2 were rated as good. Only linear scars left at the 13 donor sites, with normal blood supply to the distal limbs, and without restrictions in range of motion of knee joints nor muscle strength of quadriceps. Conclusion:The ALTPF offers advantages such as anatomical consistency, reliable blood supply and flexible combination in treatment of extensive wound of Degree Ⅳ burns in limbs. It is an ideal surgical procedure for treatment of large soft tissue defects of extremities.

Objective:To explore the diagnostic value of 5 double staining methods for tumor markers immunohistochemistry (IHC) staining combined with elastic fiber staining for the visceral pleural invasion (VPI) in lung adenocarcinoma with the maximum tumor diameter ≤ 3 cm.Methods:A retrospective case series study was conducted. Ninety paraffin-embedded VPI surgical specimens of lung adenocarcinoma with the maximum tumor diameter ≤ 3 cm diagnosed in Shanxi Province Cancer Hospital from January 2016 to January 2021 were collected. Thyroid transcription factor 1 (TTF1)+Victoria blue method+ponceau picric acid (V.G.) method, cytokeratin 7 (CK7)+resorcinol basic fuchsin method+V. G. method, AE1/AE3+Verhoeff method+V. G. method, AE1/AE3+aldehyde red method+orange G method, AE1/AE3+Victoria blue method+V. G. method were used to perform the double staining for specimens. According to the staining results, the tumor invading beyond the visceral pleural elastic fiber layer and invading the surface of visceral pleural mesothelium was diagnosed as VPI positive. The staining results and diagnostic positivity rates of VPI were compared among the 5 double staining methods for tumor markers IHC staining combined with elastic fiber staining.Results:The elastic fibers of AE1/AE3+Victoria blue method+V. G. method were blue-green, the cytoplasm of tumor cells was brown, and the collagen fibers were red. The contrast among the three was clear under the microscope, which could more intuitively display the fine structure of pleural involvement. TTF1+Victoria blue method+V.G. method showed that the elastic fibers were blue-green, and the nuclei of tumor cells were brown. Due to the fact that only the nuclei were displayed, some areas were not clearly visible, especially at the site of recurrent pleural elastic fibers; the collagen fibers were red. CK7+resorcinol basic fuchsin method+V. G. method showed purple or black purple elastic fibers, brown cytoplasm of tumor cells, and red collagen fibers; purple or black purple elastic fibers were prone to mixing with deposited black carbon powder and were difficult to identify. AE1/AE3+Verhoeff method+V. G. method showed that the elastic fibers were black and were easily mixed with deposited black carbon powder, making them difficult to identify; the cytoplasm of tumor cells was brown, and collagen fibers were red. AE1/AE3+aldehyde red method+orange G method showed that the elastic fibers were purple red, the cytoplasm of tumor cells were brown, and the collagen fibers were yellow; there was a co-staining phenomenon between elastic fibers and collagen fibers, which was difficult to identify in some cases. The positive rate of VPI diagnosing by AE1/AE3+Victoria blue method+V. G. method was 97.8% (88/90), TTF1+Victoria blue method+V. G. method was 73.3% (66/90), CK7+resorcinol basic fuchsin method+V. G. method was 72.2% (65/90), AE1/AE3+Verhoeff method+V. G. method was 58.9% (53/90), AE1/AE3+aldehyde red method+orange G method was 70.0% (63/90). The positive rate of VPI diagnosing by AE1/AE3+Victoria blue method+ V. G. method was higher than that by TTF1+Victoria blue method+V. G. method, CK7+resorcinol basic fuchsin method+V. G. method, AE1/AE3+Verhoeff method+V. G. method, and AE1/AE3+aldehyde red method+orange G method, and the differences were statistically significant ( χ2 values were 20.04, 21.04, 34.00, and 23.04, respectively, all P < 0.05). Conclusions:The AE1/AE3+Victoria blue method+V.G. method double staining method is superior to other double staining methods in diagnosing VPI in lung adenocarcinoma with the maximum tumor diameter ≤ 3 cm, and it can be used in routine work.

Objective:To explore the clinical efficacy of anterolateral thigh perforator flap (ALTPF) in treatment of extensive wound of Degree IV burns in limbs.Methods:A retrospective analysis was conducted on 9 patients who had extensive wound of Degree IV burns in limbs caused by stove burns admitted to Department of Burns and Plastic Surgery, the 988th Hospital of the Joint Logistics Support Force of the Chinese PLA between January 2017 and January 2024. Among the patients, there were 8 males and 1 female, aged between 36 and 63 years. Three patients had the wound from anterior leg to dorsal foot, 3 from leg down to ankle, 1 from forearm to hand and 2 from arm to forearm. Area of burns ranged from 20 cm × 15 cm to 30 cm × 25 cm, and all patients were treated by free ALTPF. According to whether the main artery at the recipient site was feasible for direct anastomosis with the vessels carried in flap, 4 patients were treated by bilateral parallel ALTPFs, and 5 were treated by unilateral ultra-long internally supercharged ALTPF. A total of 13 ALTPFs were harvested, with individual flap size at 20 cm × 8 cm to 46 cm × 12 cm. Donor sites were directly sutured. Time for flap harvesting, flap survival and wound healing time were records. Scheduled postoperative follow-up was conducted at outpatient clinic and via telephone interviews to evaluate functional recovery. Follow-up assessments included evaluation of flap condition, two-point discrimination (TPD), recovery of joint function at recipient sites, flap appearance and donor site recovery.Results:The time for flap harvest was 1.0 to 4.5 hours. All 13 ALTPFs successfully survived. The time from surgery to healing of recipient sites was 18 to 72 days, and all donor sites healed. Over the postoperative follow-up that lasted for 6 to 34 months, the recipient sites had found with good cosmetic outcomes, without osteomyelitis or deep tissue infection. Four ALTPFs in 2 patients were found swelling, which were revised at 6 months after surgery. Four ALTPFs in other 2 patients had pigment deposition at edges. One ALTPF was scalded, which healed after dressing changes but left with patchy scars. The remaining ALTPFs were soft, elastic, free from pain and well-perfused, with regained protective sensation at S 3. However, all of the ALTPFs failed to detect TPD. Six patients with lower limb injuries were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) ankle hindfoot scoring system: 2 patients were rated as excellent and 4 were rated as good. Three patients with upper limb injuries were evaluated using Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association: 1 patient was rated as excellent and 2 were rated as good. Only linear scars left at the 13 donor sites, with normal blood supply to the distal limbs, and without restrictions in range of motion of knee joints nor muscle strength of quadriceps. Conclusion:The ALTPF offers advantages such as anatomical consistency, reliable blood supply and flexible combination in treatment of extensive wound of Degree Ⅳ burns in limbs. It is an ideal surgical procedure for treatment of large soft tissue defects of extremities.

Objective:To explore the clinical efficacy of the first dorsal metatarsal artery pedicled lateral toe bilobed flap in repairing the finger pulp defects of two adjacent fingers.Methods:This study was a retrospective observational study. From January 2018 to December 2022, 9 patients with finger pulp defects in two adjacent fingers who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 6 males and 3 females, aged 26 to 48 years. The injured fingers were the index finger and middle finger (5 cases) or the middle finger and ring finger (4 cases). After debridement, the wound area of a single finger ranged from 1.2 cm×0.8 cm to 3.2 cm×2.8 cm. The finger pulp defects of two adjacent fingers were repaired with the first dorsal metatarsal artery pedicled lateral toe bilobed flap, and the two adjacent fingers were sutured together. The area of single flap ranged from 1.5 cm×1.0 cm to 3.5 cm×3.0 cm. The wound in the flap donor site was sutured directly or repaired with full-thickness skin graft from the groin region. The finger separation surgery was performed 3 weeks after surgery. The survival and blood supply of flaps, and survival of skin grafts and wound healing of the donor sites were observed after surgery. During follow-up, the texture, sliding, and shape of the flap, movement function of the finger, and the shape and function of the foot donor site were observed. At the last follow-up, the sensory of the flap was evaluated according to the sensory evaluation standard of the British Medical Research Council, and the hand function was evaluated according to the functional evaluation trial standard for severed finger replantation of the Hand Surgery Society of the Chinese Medical Association. Results:After surgery, all the flaps of 9 patients survived without vascular crisis. The flaps were soft in texture and good in shape. One patient had partial necrosis at the edge of the skin graft in the toe, and the wound healed after dressing change; the skin grafts in the toe in the other 8 patients survived, and the wounds healed well. During follow-up of 12 to 18 months after surgery, the flaps had soft texture, good elasticity, low sliding, and good shape. The finger movement function was normal. The wound in foot donor site recovered well without ulceration and deformity, and walking was not affected. At the last follow-up, the sensation of the flaps was sensitive, of which 8 flaps reached S3 and 10 flaps reached S3 + in sensation, and the two-point discrimination distance of the flaps was 9-13 mm. The functional scores of the affected fingers were 85 to 95, all of which were excellent. Conclusions:The first dorsal metatarsal artery pedicled lateral toe bilobed flap can repair finger pulp defects of two adjacent fingers at the same time, and the appearance, sensation, and function of the affected fingers recovered well after surgery, with less damage to the foot donor site. It is one of good methods to repair finger pulp defects of two adjacent fingers in clinic.

Objective:To explore the diagnostic value of 5 double staining methods for tumor markers immunohistochemistry (IHC) staining combined with elastic fiber staining for the visceral pleural invasion (VPI) in lung adenocarcinoma with the maximum tumor diameter ≤ 3 cm.Methods:A retrospective case series study was conducted. Ninety paraffin-embedded VPI surgical specimens of lung adenocarcinoma with the maximum tumor diameter ≤ 3 cm diagnosed in Shanxi Province Cancer Hospital from January 2016 to January 2021 were collected. Thyroid transcription factor 1 (TTF1)+Victoria blue method+ponceau picric acid (V.G.) method, cytokeratin 7 (CK7)+resorcinol basic fuchsin method+V. G. method, AE1/AE3+Verhoeff method+V. G. method, AE1/AE3+aldehyde red method+orange G method, AE1/AE3+Victoria blue method+V. G. method were used to perform the double staining for specimens. According to the staining results, the tumor invading beyond the visceral pleural elastic fiber layer and invading the surface of visceral pleural mesothelium was diagnosed as VPI positive. The staining results and diagnostic positivity rates of VPI were compared among the 5 double staining methods for tumor markers IHC staining combined with elastic fiber staining.Results:The elastic fibers of AE1/AE3+Victoria blue method+V. G. method were blue-green, the cytoplasm of tumor cells was brown, and the collagen fibers were red. The contrast among the three was clear under the microscope, which could more intuitively display the fine structure of pleural involvement. TTF1+Victoria blue method+V.G. method showed that the elastic fibers were blue-green, and the nuclei of tumor cells were brown. Due to the fact that only the nuclei were displayed, some areas were not clearly visible, especially at the site of recurrent pleural elastic fibers; the collagen fibers were red. CK7+resorcinol basic fuchsin method+V. G. method showed purple or black purple elastic fibers, brown cytoplasm of tumor cells, and red collagen fibers; purple or black purple elastic fibers were prone to mixing with deposited black carbon powder and were difficult to identify. AE1/AE3+Verhoeff method+V. G. method showed that the elastic fibers were black and were easily mixed with deposited black carbon powder, making them difficult to identify; the cytoplasm of tumor cells was brown, and collagen fibers were red. AE1/AE3+aldehyde red method+orange G method showed that the elastic fibers were purple red, the cytoplasm of tumor cells were brown, and the collagen fibers were yellow; there was a co-staining phenomenon between elastic fibers and collagen fibers, which was difficult to identify in some cases. The positive rate of VPI diagnosing by AE1/AE3+Victoria blue method+V. G. method was 97.8% (88/90), TTF1+Victoria blue method+V. G. method was 73.3% (66/90), CK7+resorcinol basic fuchsin method+V. G. method was 72.2% (65/90), AE1/AE3+Verhoeff method+V. G. method was 58.9% (53/90), AE1/AE3+aldehyde red method+orange G method was 70.0% (63/90). The positive rate of VPI diagnosing by AE1/AE3+Victoria blue method+ V. G. method was higher than that by TTF1+Victoria blue method+V. G. method, CK7+resorcinol basic fuchsin method+V. G. method, AE1/AE3+Verhoeff method+V. G. method, and AE1/AE3+aldehyde red method+orange G method, and the differences were statistically significant ( χ2 values were 20.04, 21.04, 34.00, and 23.04, respectively, all P < 0.05). Conclusions:The AE1/AE3+Victoria blue method+V.G. method double staining method is superior to other double staining methods in diagnosing VPI in lung adenocarcinoma with the maximum tumor diameter ≤ 3 cm, and it can be used in routine work.

Objective:To investigate the genotype and epidemiological characteristics of human metapneumovirus (HMPV) among hospitalized cases with acute respiratory infections (ARI) in children in Changchun City, Jilin Province, China.Methods:From June 2019 to June 2023, throat swabs of ARI inpatients in Changchun Children′s Hospital were collected, and their epidemiological and clinical information were also collected. Quantitative reverse transcription-PCR was used to identify HMPV-positive cases, followed by the amplification of the G gene and genetic analysis in the HMPV-positive cases.Results:A total of 3 311 children hospitalized with ARI were included in this study. Their age ranged from 0 to 17 years old, and the M ( Q1, Q3) of age was 2 (1, 3) years. About 1 811 (54.70%) cases were males. A total of 167 HMPV-positive cases were detected with a positive rate of 5.04%, of which 92.81% (155/167) were children under 5 years old. The positive rate of HMPV in 2019 was 6.37% (30/471), which dropped to the lowest in 2020 (2.31%, 10/432). The HMPV-positive rate was then rebounded in 2021 (4.70%, 60/1 277) and 2022 (4.56%, 21/461), which increased to 6.87% (46/670) in 2023. The difference in HMPV-positive rate among each year was statistically significant ( P<0.05). The prevalence peak of HMPV varied in different years, showing either a unimodal or bimodal distribution in one year. A total of 79 HMPV G gene sequences were obtained, of which subtype A and subtype B accounted for 48.10% and 51.90%, respectively. All of the subtype A sequences were clarified as A2c duplicated variants, and subtype B was mainly B2 genotype. Besides, subtypes A and B were prevalent alone or co-circulated in different years, and there was a subtype replacement pattern in HMPV. Conclusion:The positive rate of HMPV in hospitalized ARI cases in children is significantly different from 2019 to 2023 in Changchun City. Notably, there are certain switch patterns of HMPV subtypes A and B in different years.

Objective:To investigate the genotype and epidemiological characteristics of human metapneumovirus (HMPV) among hospitalized cases with acute respiratory infections (ARI) in children in Changchun City, Jilin Province, China.Methods:From June 2019 to June 2023, throat swabs of ARI inpatients in Changchun Children′s Hospital were collected, and their epidemiological and clinical information were also collected. Quantitative reverse transcription-PCR was used to identify HMPV-positive cases, followed by the amplification of the G gene and genetic analysis in the HMPV-positive cases.Results:A total of 3 311 children hospitalized with ARI were included in this study. Their age ranged from 0 to 17 years old, and the M ( Q1, Q3) of age was 2 (1, 3) years. About 1 811 (54.70%) cases were males. A total of 167 HMPV-positive cases were detected with a positive rate of 5.04%, of which 92.81% (155/167) were children under 5 years old. The positive rate of HMPV in 2019 was 6.37% (30/471), which dropped to the lowest in 2020 (2.31%, 10/432). The HMPV-positive rate was then rebounded in 2021 (4.70%, 60/1 277) and 2022 (4.56%, 21/461), which increased to 6.87% (46/670) in 2023. The difference in HMPV-positive rate among each year was statistically significant ( P<0.05). The prevalence peak of HMPV varied in different years, showing either a unimodal or bimodal distribution in one year. A total of 79 HMPV G gene sequences were obtained, of which subtype A and subtype B accounted for 48.10% and 51.90%, respectively. All of the subtype A sequences were clarified as A2c duplicated variants, and subtype B was mainly B2 genotype. Besides, subtypes A and B were prevalent alone or co-circulated in different years, and there was a subtype replacement pattern in HMPV. Conclusion:The positive rate of HMPV in hospitalized ARI cases in children is significantly different from 2019 to 2023 in Changchun City. Notably, there are certain switch patterns of HMPV subtypes A and B in different years.

In order to achieve the purpose of rapid detection of duck astrovirus type 1(DAstV-1),specific primers were designed based on the conservative region of ORF1a which belonged to DAstV-1(WF1202 strain).A real-time fluorescent quantitative PCR(qPCR)detective method for DAstV-1 was established.Clinical samples were detected by the qPCR method and the positive samples were used for virus isolation and identification.Results showed that the detection limit of the established method was 4.64×103 copies/μL,which was 10 times higher than the normal RT-PCR method.In addition,no cross-reactions were found with other common infectious disease pathogens in poultry,indicating that the qPCR method had good specificity.What's more,the coef-ficient of variations(Cv)in intra-and inter-assays were 0.85％-2.85％and 0.21％-2.94％,re-spectively,both less than 3％,indicating that the qPCR method had a good repeatability.Using this method,35 tissue samples from different duck farms in 10 provinces from 2020 to 2022 were detected for DAstV-1.Results showed that the positive rate was 25.71％(9/35),and the coinci-dence rate was 94.29％when compared with the normal RT-PCR method.A positive sample ran-domly taken for the virus isolation through duck embryo passage,and the allantoic fluid was col-lected and then was verified by the qPCR method and inoculated with 1-day-old healthy ducklings for the animal regression experiment.The infected ducklings suffered from transient disease but did not die.The liver tissues were all positive with DAstV-1 when detected by qPCR.Meanwhile,autopsy showed that there were slight changes in the livers,and the histopathological observation showed that the liver cells were steatosis.These findings indicated that the isolated DAstV-1 strain had weak pathogenicity and might be a low virulent strain.To sum up,the qPCR detection method of DAstV-1 was successfully established in this work,and could provide technical support for clini-cal diagnosis,isolation and identification,and molecular epidemiology monitoring of DAstV-1.