Fingertip injuries often involve the loss of skin, soft tissue, and sometimes even phalange, seriously affecting the patient's hand function and appearance. Therefore, fingertip reconstruction requires both functional recovery and aesthetics. And how to better restore fingertip defect has become an issue that hand surgeons should continue to explore. In recent years, free flaps have made remarkable progress in the field of fingertip repair, and free flaps such as radial artery superficial palmar branch free flap, free thenar flap and free toe flap provide a variety of effective methods to solve the problem. By referring to the literatures on free flap in fingertip repair, this paper summarises the application status and research progress of free flap in fingertip defect reconstruction, providing a reference for personalised treatment of patients with fingertip defect.

Objective To comprehensively understand the dynamic transcriptional landscape during infection through investigating the temporal molecular changes in macrophages RAW 264.7 upon infection with Salmonella typhimurium SL1344.Methods Macrophages RAW 264.7 were infected with Salmonella typhimurium SL1344,and cell samples were collected at 0 h,8 h,and 16 h for RNA-sequencing(RNA-seq).Upstream and downstream analyses of the transcriptome data including differential gene expression,clustering,functional annotation,and mo-lecular network studies were conducted to elucidate the signaling pathways changes in macrophages.Results Infec-ted macrophages exhibited significant morphological and transcriptional changes.Differential gene analysis identified significant upregulation and downregulation patterns.Clustering revealed six gene clusters involving various signaling pathways,such as immune response,membrane transport,and lipid catabolic process.Conclusions Macrophages dynamically respond to Salmonella typhimurium infection,displaying distinct temporal gene expression patterns.The coordinated activation of immune response,membrane transport,and lipid catabolic process pathways implies a multifaceted cellular adaptation to external infections,providing essential insights into the molecular mechanisms of macrophage response to Salmonella typhimurium infection.

Kashin-Beck disease (KBD) is a chronic endemic bone and joint disease, with severe cases of short stature, joint deformities, and significantly reduced quality of life. Its etiology is currently unclear. Matrix metalloproteinases (MMPs) are endopeptidases that can degrade the extracellular matrix of articular cartilage cells, and are closely related to the occurrence and development of bone and joint diseases. At present, some scholars have found that MMPs can cause cartilage damage in KBD patients and promote the progression of KBD, but its specific mechanism of action is still unclear. This article reviews the research progress on the etiology of KBD, MMPs and its related genes, and their relationship with KBD cartilage injury both domestically and internationally. In order to provide theoretical support for in-depth research on the pathogenesis of KBD and to improve and update its treatment methods.

Objective:To investigate the efficacy of 3D-printed quantitative bone implants assisting second-stage Masquelet technique for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures.Methods:A retrospective case series analysis was made on 26 patients with long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures treated in Wuxi Ninth People′s Hospital from July 2015 to December 2020, including 20 males and 6 females; aged 19-63 years [(46.5±4.5)years]. Gustilo classification was type IIIB in 23 patients and type IIIC in 3. In the first stage, all patients had thoroughly emergent debridement, removal of all free bone pieces, restoration of the length and force line plus externally fixion, and vacuum sealing drainage (VSD) of the residual wound. After 2-7 days, the external fixation was removed and replaced by internal fixation, with the bone cement filling in the defect area and the free flap covering the wound. The length of tibial bone defect was 5-14 cm [(6.3±0.4)cm], and the tibial defect volume was 12.2-73.1 cm 3 [(33.6±9.2)cm 3]. In the second stage (6-19 weeks after injury), the bone cement was removed, followed by autologous bone grafting. Prior to bone grafting, digital technology was used to accurately calculate the bone defect volume, and an equal volume of bone harvesting area was designe to produce the 3D printed osteotomy template. Bone grafting was conducted after bone removal according to the osteotomy template during operation. The success rate of one-time iliac bone extraction, bone harvesting time, and bleeding volume were recorded. Pain in the bone extraction area was evaluated by visual analogue score (VAS) at 1 day and 1 month after operation and at the last follow-up. Wound healing, complications, and bone healing were observed. Life quality was evaluated by health survey brief form (SF-36) including scores of physical component summary (PCS) and mental component summary (MCS) before bone grafting and at the last follow-up. Results:All the patients were followed up for 13-53 months [(32.3±12.5)months]. One-time iliac bone extraction was successful in all the patients. Bone harvesting time was 15-30 minutes [(21.0±2.5)minutes]. The bleeding volume was 50-120 ml [(62.3±29.0)ml]. The VAS was 1-4 points [(1.2±0.9)points] at 1 day after operation, higher than these (0.0±0.0)points at 1 month after operation and at the last follow-up (all P<0.01). Totally, 25 patients obtained wound healing after operation, except for 1 patient with superficial wound infection after bone grafting that was healed by dressing change. There was 1 patient with bone infection after 3 months of bone grafting that was healed by repeated surgery with Masquelet technique in the first and second stage. Besides, 2 patients had symptoms of cutaneous nerve injury in the iliac donor area. The time of bone healing was 4-7 months [(5.8±0.8)months]. The scores of PCS and MCS in SF-36 at the last follow-up were (73.6±12.8)points and (83.6±13.2)points, significantly higher than those before bone grafting [(46.8±0.5)points, (60.7±2.0)points] (all P<0.01). Conclusion:Second-stage Masquelet technique with 3D printed quantitative bone implants for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures is associated with shortened bone harvesting time, attenuated pain, reduced complications, accelerated bone healing and improved function.

Objective:To identify the genetic variation in a mucopolysaccharidosis type Ⅱ(MPS Ⅱ)family, and conduct a functional study of iduronate-2-sulfatase(IDS): c.323A>C.Methods:A five-generation MPS Ⅱ family of 83 individuals including 4 patients from northern China was collected. Urine mucopolysaccharide and Alder-Reilly body were tested to assist the clinical diagnosis of MPS Ⅱ. IDS enzyme activity was detected on core family members. By the whole exome sequencing of a MPS Ⅱ patient in this family and bioinformatics analysis, the variant was screened and further identified by PCR-Sanger sequencing. Finally, to validate the function of the variant in vitro, the wild-type IDS overexpression plasmid(pCMV-hIDS-WT)and the IDS overexpression plasmid carrying the mutation site(pCMV-hIDS-c.323A>C)were transfected into COS-7 cells and the IDS activity was detected. Results:The proband(Ⅳ3)and Ⅳ4 were diagnosed as MPS Ⅱ by urine mucopolysaccharide, Alder-Reilly body, and IDS enzyme activity tests. Ⅳ3, Ⅳ4, Ⅲ19, and Ⅲ32 were determined to carry IDS: c.323A>C missense variant through the whole-exome sequencing, and diagnosed as MPS Ⅱ. Meanwhile, Ⅱ2, Ⅱ4, Ⅱ8, Ⅱ12, Ⅱ14, Ⅲ5, Ⅲ7, Ⅳ14 in the MPS Ⅱ family carried IDS: c.323A>C missense variant, and were excluded as MPS Ⅱ. The in vitro experiment in COS-7 cells showed that the missense mutation led to a significant decrease in IDS enzyme activity. Conclusion:The variant IDS: c.323A>C: p.Y108S significantly decreases the activity of IDS enzyme in vivo and in vitro, and it is identified as a pathogenic variant for MPS Ⅱ.

【Objective】 Until now, most clinical and basic studies on Kashin-Beck disease (KBD) have focused on the visible deformed extremities, and there is a lack of reports concerning their spinal features, especially for the atlantoaxial joint. The purpose of this study was to determine the prevalence and radiographic features of atlantoaxial dislocation (AAD) in KBD in adult patients. 【Methods】 The prevalence and radiographic features of AAD were determined by the basic information collected, clinical symptoms, and lateral and dynamic plain radiography in 111 KBD patient and 120 non-KBD participants. In the KBD group, AAD and non-AAD patients were compared in age, gender, height, weight, BMI, smoking history, chronic history, disease duration and grade of disease so as to identify the related factors of the occurrence of AAD. 【Results】 Symptoms at the neck or neurological manifestations were present in 17.5% (21/120) in the non-KBD population and 39.6% (44/111) patients with KBD. AAD case was not detected in the non-KBD population, while in 16.2% (18/111) of KBD patients in the endemic area. The prevalence was higher in the KBD patients than in the non-KBD population, and there was a significant difference in the detection rate of AAD between the two groups (χ²=21.10, P<0.001). Plain radiography demonstrated that there were 10 (55.6%) cases with separation of the odontoid process and the other 8 (44.4%) cases with hypoplasia of odontoid process. Anterior AAD was noted in 12 (66.7%) patients and posterior AAD in 6 (33.3%) cases based on the displacement direction, while 16 (88.9%) cases were reducible and 2 (11.1%) cases were irreducible on the basis of the reducibility. Comparing the 93 patients with non-AAD KBD patients and 18 patients with AAD patients, there was no significant difference in age, sex, BMI, history of medical disease or smoking (all P>0.05). There were significant differences in height, weight, disease duration and grade of disease between AAD and non-AAD patients (all P<0.05). 【Conclusion】 KBD can cause the occurrence of atlantoaxial dislocation by inducing separation or hypoplasia of the odontoid process. This research may provide clinical evidence for screening, earlier prevention and treatment of atlantoaxial dislocation in adult KBD patients.

Objective:To explore the effect of social skill training on the frustration and self-esteem of schizophrenics.Methods:From December 2020 to May 2021, 100 schizophrenics hospitalized in the same ward of the Huai'an Third People's Hospital of Jiangsu Province were selected as the research object by convenience sampling. The patients were randomly divided into the control group and the observation group with 50 cases each. The control group received routine nursing, while the observation group carried out social skills training on the basis of the control group. Before and 8 weeks after the intervention, the frustration, self-esteem and social function of the patients in the two groups were evaluated with the Defeat Scale (DS), Rosenberg Self-esteem Scale (SES) and the Scale of Social Function in Psychosis Inpatients (SSPI) .Results:Before intervention, there was no statistical difference in scores of frustration, self-esteem and social function between the two groups ( P>0.05). After intervention, the scores of frustration in the two groups were lower than those before intervention, and the scores in the observation group were lower than those in the control group, with statistical differences ( P<0.01). The scores of self-esteem and social function in the two groups were higher than those before intervention, and the scores in the observation group were higher than those in the control group, with statistical differences ( P<0.05) . Conclusions:Social skill training can improve the mental state of schizophrenics, reduce their frustration, adjust their self-esteem, and improve their social functions.

Objective:To explore the latest progress of oncology drug clinical trials in China under COVID-19, as well as to provide decision-making evidence for related stakeholders. Research progress of oncology drug trials and approved cancer drugs in China in 2020 were systematically summarized and compared with 2019.Methods:Information Disclosure Platform for Drug Clinical Studies and China Food and Drug Administration Query System for Domestic and Imported Drug were searched for registered clinical trials and approved oncology drugs, respectively. The trial scope, stage, drug type, effect and mechanism of domestic and global pharmaceutical enterprises were compared between 2019 and 2020.Results:A total of 722 cancer drug trials registered in China in 2020, with an annual growth rate of 52.3%, accounting for 28.3% of all registered trials. Among them, 603 (83.5%) trials were initiated by domestic pharmaceutical enterprises, and 105 (14.5%) were international multicenter trials, phase I trials accounted for 44.5%. For all those trials, there were 458 cancer drug varieties, with an annual growth rate of 36.7%, and 361 (85.8%) were developed by domestic enterprises. Most of the investigational products were therapeutic innovative drugs (77.1%), major in tumor treatment (92.8%). In terms of mechanism, targeted drugs were the most popular, accounting for 76.6%, and programmed cell death-1 (PD-1) and epithelial growth factor receptor (EGFR) were the most common targets. In addition, there were 19 anticancer drugs from 17 companies approved in China in 2019, with 10 drugs from domestic companies. Lung cancer and breast cancer are the most common indications for both registered trials and marketed drugs. No statistically significant differences were found between 2020 and 2019 in terms of the distribution of trial sponsor, scope and stage, as well as the distribution of drug type, effect and mechanism ( P>0.05). Conclusions:During the Covid-19 epidemic period, clinical trials of oncology drugs in China progress smoothly and maintain a high growth rate. Series of innovative products obtained by domestic enterprises in 2020 is the main driving force of development of oncology drug clinical trials in China.

Objective:To explore the advantages, disadvantages, and precautions of clinically applying four types of non-trunk vessels as recipient vessels in the free flap transplantation for repairing peri-knee wounds.Methods:A retrospective analysis of the clinical data was conducted of 23 patients (12 males and 11 females) with peri-knee skin and soft tissue defects who underwent free anterolateral thigh flaps or free latissimus dorsi flaps. The patients were admitted to the Department of Traumatic Orthopedics, Wuxi 9th People’s Hospital, from January 2015 to December 2019. The patients were aged 20-72 years (mean 41.9). The wound size with vital tissue exposure was 18.0 cm×5.0 cm-42.0 cm×9.0 cm. Preoperative color Doppler and computerized tomography angiography techniques were used to assist in positioning and to measure the recipient vessels (including the descending genicular vessel, descending branch of the lateral femoral circumflex vessel, the medial sural vessel, and the medial inferior genicular vessel) and blood vessels in the donor area (including descending branches of lateral femoral circumflex vessels and thoracic dorsal vessels). The caliber was measured and verified by a soft ruler with a scale intraoperative. The measured values of the caliber were recorded in the preoperative and intraoperative. The color and texture of the two flaps and the healing of the donor sites were observed postoperatively. The conformance ratio of preoperative and intraoperative measured values of vessels in the donor and recipient areas (except for the only case of the medial inferior genicular vessel) was compared. SPSS 26.0 software was used for data analysis. The measurement data were showed as Mean±SD, and the comparison results were analyzed by paired t-test. P<0.05 was considered statistically significant. Results:A total of 23 patients with skin and soft tissue defects around the knee were enrolled. The size of the tissue flap was 18.0 cm×5.0 cm-46.0 cm×9.0 cm. Twelve of 14 anterolateral thigh flaps anastomosed to the descending genicular vessel survived. The remaining two cases had a length of 6 cm and 4 cm necrosis at the distal flap, which was finally given skin-grafting and healed. One of the 12 survived flaps failed in limb salvage in Phase Ⅰ and was thus given flap reconstruction in Phase Ⅱ. Another case was given amputation due to serious infection of limbs, with incomplete ends of the survived flaps rotated and covered. In four cases anastomosed to the descending branch of the lateral circumflex femoral vessel, three anterolateral thigh flaps survived completely, and one distal latissimus dorsi flap had a length of 12 cm necrosis which was given debridement and Ilizarov bone transport for heal. Two anterolateral thigh flaps and two latissimus dorsi flaps anastomosed to the medial sural vessel survived completely, of which one anterolateral thigh flap had vein crisis which was later solved. The anterolateral thigh flap of 1 case anastomosed to medial inferior genicular vessels completely survived. The postoperative follow-up lasted 3-30 months with an average of 13.6 months. All the flaps have good color and textures with good incision heal at the donor site in Phase Ⅰ. There was no statistically significant difference in the preoperative and intraoperative measurement values of blood vessel caliber in the donor and recipient areas ( P>0.05). Conclusions:Four non-trunk peri-knee blood vessels can serve as recipient vessels of the free tissue flaps, and proper selection of the vessels can effectively improve the survival rate of the tissue flaps. The descending genicular vessel can serve as the recipient vessel for a priority, as with a superficial position, fixed dissection, simple positioning, and convenient intraoperative dissection.

Objective:To explore the advantages, disadvantages, and precautions of clinically applying four types of non-trunk vessels as recipient vessels in the free flap transplantation for repairing peri-knee wounds.Methods:A retrospective analysis of the clinical data was conducted of 23 patients (12 males and 11 females) with peri-knee skin and soft tissue defects who underwent free anterolateral thigh flaps or free latissimus dorsi flaps. The patients were admitted to the Department of Traumatic Orthopedics, Wuxi 9th People’s Hospital, from January 2015 to December 2019. The patients were aged 20-72 years (mean 41.9). The wound size with vital tissue exposure was 18.0 cm×5.0 cm-42.0 cm×9.0 cm. Preoperative color Doppler and computerized tomography angiography techniques were used to assist in positioning and to measure the recipient vessels (including the descending genicular vessel, descending branch of the lateral femoral circumflex vessel, the medial sural vessel, and the medial inferior genicular vessel) and blood vessels in the donor area (including descending branches of lateral femoral circumflex vessels and thoracic dorsal vessels). The caliber was measured and verified by a soft ruler with a scale intraoperative. The measured values of the caliber were recorded in the preoperative and intraoperative. The color and texture of the two flaps and the healing of the donor sites were observed postoperatively. The conformance ratio of preoperative and intraoperative measured values of vessels in the donor and recipient areas (except for the only case of the medial inferior genicular vessel) was compared. SPSS 26.0 software was used for data analysis. The measurement data were showed as Mean±SD, and the comparison results were analyzed by paired t-test. P<0.05 was considered statistically significant. Results:A total of 23 patients with skin and soft tissue defects around the knee were enrolled. The size of the tissue flap was 18.0 cm×5.0 cm-46.0 cm×9.0 cm. Twelve of 14 anterolateral thigh flaps anastomosed to the descending genicular vessel survived. The remaining two cases had a length of 6 cm and 4 cm necrosis at the distal flap, which was finally given skin-grafting and healed. One of the 12 survived flaps failed in limb salvage in Phase Ⅰ and was thus given flap reconstruction in Phase Ⅱ. Another case was given amputation due to serious infection of limbs, with incomplete ends of the survived flaps rotated and covered. In four cases anastomosed to the descending branch of the lateral circumflex femoral vessel, three anterolateral thigh flaps survived completely, and one distal latissimus dorsi flap had a length of 12 cm necrosis which was given debridement and Ilizarov bone transport for heal. Two anterolateral thigh flaps and two latissimus dorsi flaps anastomosed to the medial sural vessel survived completely, of which one anterolateral thigh flap had vein crisis which was later solved. The anterolateral thigh flap of 1 case anastomosed to medial inferior genicular vessels completely survived. The postoperative follow-up lasted 3-30 months with an average of 13.6 months. All the flaps have good color and textures with good incision heal at the donor site in Phase Ⅰ. There was no statistically significant difference in the preoperative and intraoperative measurement values of blood vessel caliber in the donor and recipient areas ( P>0.05). Conclusions:Four non-trunk peri-knee blood vessels can serve as recipient vessels of the free tissue flaps, and proper selection of the vessels can effectively improve the survival rate of the tissue flaps. The descending genicular vessel can serve as the recipient vessel for a priority, as with a superficial position, fixed dissection, simple positioning, and convenient intraoperative dissection.