Objective: To summarize the clinical experience of expanded internal mammary artery perforator (IMAP) flap combined with vascular supercharge in reconstruction of faciocervical scar. Methods: The retrospective observational study was conducted. From September 2012 to May 2021, 23 patients with postburn or posttraumatic faciocervical scars who met the inclusion criteria were admitted to Shanghai Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine, including 18 males and 5 females, aged from 11 to 58 years, all of whom were reconstructed with expanded IMAP flaps. At the first stage, one or two skin and soft tissue expander (s) with appropriate rated capacity were implanted in the anterior chest area according to the location and size of the scars. The IMAP, thoracic branch of supraclavicular artery, and lateral thoracic artery were preserved during the operation. The skin and soft tissue expanders were inflated with normal saline after the operation. The flaps were transferred during the second stage. The dominant IMAP was determined preoperatively using color Doppler ultrasound (CDU) blood flow detector. The faciocervical scars were removed, forming wounds with areas of 9 cm×7 cm-28 cm×12 cm, and the perforators of superficial temporal artery and vein or facial artery and vein were preserved during the operation. The flaps were designed according to the area and size of the wounds after scar resection with the dominant IMAP as the pedicle. Single-pedicle IMAP flaps were used to repair small and medium-sized wounds. For larger defects, the blood perfusion areas of vessels in the anterior chest were evaluated by indocyanine green angiography (ICGA). In situations where the IMAP was insufficient to nourish the entire flap, double-pedicle flaps were designed by using the thoracic branch of supraclavicular artery or lateral thoracic artery for supercharging. Pedicled or free flap transfer was selected according to the distance between the donor areas and recipient areas. After transplantation of flaps, ICGA was conducted again to evaluate blood perfusion of the flaps. The donor sites of flaps were all closed by suturing directly. Statistics were recorded, including the number, rated capacity, normal saline injection volume, and expansion period of skin and soft tissue expanders, the location of the dominant IMAP, the total number of the flaps used, the number of flaps with different types of vascular pedicles, the flap area, the flap survival after the second stage surgery, the occurrence of common complications in the donor and recipient areas, and the condition of follow-up. Results: Totally 25 skin and soft tissue expanders were used in this group of patients, with rated capacity of 200-500 mL, normal saline injection volume of 855-2 055 mL, and expansion period of 4-16 months. The dominant IMAP was detected in the second intercostal space (20 sides) or the third intercostal space (5 sides) before surgery. A total of 25 expanded flaps were excised, including 2 pedicled IMAP flaps, 11 free IMAP flaps, 4 pedicled thoracic branch of supraclavicular artery+free IMAP flaps, and 8 free IMAP+lateral thoracic artery flaps, with flap areas of 10 cm×8 cm-30 cm×14 cm. After the second stage surgery, tip necrosis of flaps in three patients occurred, which healed after routine dressing changes; one patient developed arterial embolism and local torsion on the vascular pedicle at the anastomosis of IMAP and facial artery, and the blood supply recovered after thrombectomy and vascular re-anastomosis. Fourteen patients underwent flap thinning surgery in 1 month to 6 months after the second stage surgery. The follow-up for 4 months to 9 years showed that all patients had improved appearances of flaps and functions of face and neck and linear scar in the donor sites of flaps, and one female patient had obvious nipple displacement and bilateral breast asymmetry. Conclusions: The expanded IMAP flap is matched in color and texture with that of the face and neck, and its incision causes little damage to the chest donor sites. When combined with vascular supercharge, a double-pedicle flap can be designed flexibly to further enhance the blood supply and expand the flap incision area, which is a good choice for reconstruction of large faciocervical scar.
China ; Cicatrix/surgery* ; Female ; Humans ; Male ; Mammary Arteries/surgery* ; Perforator Flap ; Reconstructive Surgical Procedures ; Saline Solution ; Skin Transplantation ; Soft Tissue Injuries/surgery* ; Surgical Wound ; Treatment Outcome

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG _FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG _EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG _MM-PBSA or ΔG _MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC₅₀ of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.

Objective:To clarify the influence and influence paths of stigma on the time of the healthcare-seeking decision in caregivers of elderly patients with dementia, and to provide a theoretical basis for the construction of corresponding humanistic care strategies.Methods:A total of 176 caregivers of elderly patients with dementia who visited the Affiliated Hospital of Xuzhou Medical University and Xuzhou Oriental People ′s Hospital from February 2021 to February 2022 were selected as the study subjects. The General Information Questionnaire, self-designed Scale of Stigma for Caregivers of Senile dementia patients, Multidimensional Scale of Perceived Social Support, self-designed Elderly Dementia Caregivers′ Perceived Barriers Scale for Healthcare-seeking Decision, and self-designed Scale of the Intention to Seek Healthcare for caregivers of senile dementia patients were used in the survey. AMOS 20.0 was used to establish a structural equation model for path analysis. Results:The higher the stigma of caregivers, the longer the time of the healthcare-seeking decision ( β=0.05, P<0.05). Social support, perceived barriers to the healthcare-seeking decision, and the intention to seek healthcare were the mediating variables of caregivers ′ stigma affecting the time of the healthcare-seeking decision, with a total effect of -0.04, 0.14, and 0.36, respectively, and all P<0.05. Conclusions:The stigma in caregivers of senile dementia patients is an important factor affecting the time of the healthcare-seeking decision. By improving mediating factors including social support, perceived barriers to the healthcare-seeking decision, and the intention to seek healthcare, the implementations of targeted humanistic care strategies are expected to help shorten the time of the healthcare-seeking decision.

Due to the limited resource of bear bile powder, the major raw material of Tanreqing Capsules(TRQ), cultured bear bile powder is used as a replacement to develop the Tanreqing Capsules Substitute(TRQS). An LC-MS/MS method was established in this study for simultaneous quantitation of 8 compounds from TRQS in rat plasma: tauroursodeoxycholic acid(TUDCA), taurocheno-deoxycholic acid(TCDCA), ursodeoxycholic acid(UDCA), chenodeoxycholic acid(CDCA), ferulic acid, wogonoside, baicalin, and forsythoside A. Thereby, the pharmacokinetic behaviors of TRQ and TRQS were evaluated. Concentration of endogenous compounds TUDCA, TCDCA, UDCA, and CDCA was determined with the stable isotope surrogate analytes: D4-TUDCA, D4-TCDCA, D4-UDCA, and D4-CDCA. Plasma samples were extracted by acetonitrile-induced protein precipitation. The LC conditions are as follows: Waters BEH C_(18) column(2.1 mm×100 mm, 1.7 μm), mobile phase of 10 mmol·L~(-1) ammonium formate aqueous solution(containing 0.01% formic acid) and acetonitrile-methanol mixture(1∶5). MS conditions are as below: multiple reaction monitoring(MRM), ESI~(+/-). Concentration of UDCA, CDCA, TUDCA, and TCDCA was corrected with a response factor, which is the ratio between the responses recorded for the surrogate and the authentic analyte at the equal concentration. Each of the plasma components showed good linearity(r > 0.995 1). Accuracy and precision met the criteria(inter-day RSD<7.0%, RE 89.98%-112.0%; intra-day RSD<12%, RE 90.41%-111.2%). The recovery was 64.83%-119.9% and matrix effect was 87.15%-113.8%. The validated method was applied for pharmacokinetic study of TRQS and TRQ(po, 0.94 g·kg~(-1)). There was no significant difference in C_(max) and AUC_(0-24 h) of baicalin, UDCA, TUDCA, and TCDCA between the two groups, indicating similar pharmacokinetic behaviors between TRQS and TRQ in rats.
Animals ; Capsules ; Chromatography, Liquid ; Drugs, Chinese Herbal/pharmacokinetics* ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry

China/epidemiology* ; Coronary Angiography ; Coronary Artery Disease/epidemiology* ; Cross-Sectional Studies ; Humans ; Risk Assessment ; Risk Factors

Objective:To investigate the effect of indocyanine green angiography (ICGA) in the design of pre-expanded perforator flaps in the reconstruction of large defects.Methods:From October 2018 to October 2019, there were 22 patients undergoing facial and cervical reconstructive surgeries based on pre-expanded perforator flaps in the back region in Shanghai Ninth Peoples′ Hospital. 12 male and 10 female patients, ranging from 4 to 26 years old with an average age of 19, were all suffered from inferior facial and cervical defects after burns. Single-pedicled or multi-pedicled perforator flaps from back region were designed for treatment. ICGA was conducted after flap dissection intra-operatively to evaluate perfusion areas of perforators, which helped surgeons to determine whether supercharging should be conducted. After flap transplantation, ICGA was conducted again to evaluate the blood supply. Statistics of post-operative complications such as flap necrosis were collected.Results:the average flap size was 27 cm ×17 cm. With the guidance of ICGA, 15 cases remained the design of single pedicle including 5 superficial cervical artery (SCA) flaps and 10 free circumflex scapular artery (CSA) perforator flaps. Supercharging was performed in 7 cases: including 2 SCA flaps supercharged with CSA perforator and 5 free CSA perforator flaps supercharged with thoracodorsal artery (TDA) perforator. Venous thrombus occurred in 1 case but recovered after re-anastomosis of vessels. Except for 2 tip necroses, 20 flaps survived completely one week postoperatively. 2 tip necroses were recovered after dressing changes. All the patients were followed up for 5 to 16 months, with good flap color and texture, and improved function of head and neck.Conclusions:ICGA can be used as a safe and effective intraoperative detection method to guide the selection of appropriate perforators and the decisions on whether to conduct supercharging, which optimizes flap design and improves the success of surgery.

Objective:To investigate the effect of indocyanine green angiography (ICGA) in the design of pre-expanded perforator flaps in the reconstruction of large defects.Methods:From October 2018 to October 2019, there were 22 patients undergoing facial and cervical reconstructive surgeries based on pre-expanded perforator flaps in the back region in Shanghai Ninth Peoples′ Hospital. 12 male and 10 female patients, ranging from 4 to 26 years old with an average age of 19, were all suffered from inferior facial and cervical defects after burns. Single-pedicled or multi-pedicled perforator flaps from back region were designed for treatment. ICGA was conducted after flap dissection intra-operatively to evaluate perfusion areas of perforators, which helped surgeons to determine whether supercharging should be conducted. After flap transplantation, ICGA was conducted again to evaluate the blood supply. Statistics of post-operative complications such as flap necrosis were collected.Results:the average flap size was 27 cm ×17 cm. With the guidance of ICGA, 15 cases remained the design of single pedicle including 5 superficial cervical artery (SCA) flaps and 10 free circumflex scapular artery (CSA) perforator flaps. Supercharging was performed in 7 cases: including 2 SCA flaps supercharged with CSA perforator and 5 free CSA perforator flaps supercharged with thoracodorsal artery (TDA) perforator. Venous thrombus occurred in 1 case but recovered after re-anastomosis of vessels. Except for 2 tip necroses, 20 flaps survived completely one week postoperatively. 2 tip necroses were recovered after dressing changes. All the patients were followed up for 5 to 16 months, with good flap color and texture, and improved function of head and neck.Conclusions:ICGA can be used as a safe and effective intraoperative detection method to guide the selection of appropriate perforators and the decisions on whether to conduct supercharging, which optimizes flap design and improves the success of surgery.

Objective To investigate the value of endoscopic retrograde appendicitis therapy ( ERAT) in the diagnosis and treatment of atypical acute appendicitis. Methods All the 48 patients suspected of atypical acute appendicitis in Jiangsu Province Hospital from January 2015 to December 2016 were randomly divided into ERAT group and conservative treatment group according to the treatment method. The final appendectomy rate of the two groups was analyzed. Results Only 17 of the 24 patients in the ERAT group received endoscopic treatment because of complex conditions or personal wishes, and 16 cases were diagnosed as acute appendicitis. Surgical resection was performed in 5 cases because of recurrence of the disease after ERAT, and the appendectomy rate was 31. 2％ ( 5/16 ) . In the conservative treatment group, all 24 patients were treated with antibiotics. Twenty of them underwent surgical resection with appendectomy rate of 83. 3％ ( 20/24) , and 1 of them had appendiceal perforation. The appendectomy rate of the ERAT group was significantly lower than that of the conservative treatment group (χ2=11. 111, P<0. 05) . Conclusion ERAT has a high diagnostic and therapeutic value for atypical acute appendicitis.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) and bone marrow mononuclear cells(BMMNCs) have been both used to treat spastic cerebral palsy. However, the differences in their therapeutic effects remain unknown. OBJECTIVE: To compare the therapeutic effects of BMMSCs and BMMNCs in cerebral palsy children as well as on fine motor function. METHODS: 105 children with spastic cerebral palsy were enrolled and randomly assigned to three groups: BMMSCs group, BMMNCs group and control group. Patients in the two transplantation groups received four intrathecal cell injections, and those in the control group received Bobath therapy, twice a day, for consecutive 3 weeks. The Gross Motor Function Measure (GMFM) and Fine Motor Function Measure (FMFM) were used to evaluate the therapeutic efficacy at 3, 6 and 12 months after transplantation. RESULTS AND CONCLUSION: At 3 months after cell transplantation, scores in A dimension of GMFM and in A, C dimensions of FMFM in BMMSC group were all superior to those of BMMNC group and control group (P < 0.05). At 6 months after cell transplantation, scores in A, B dimensions of GMFM and in A, B, C, D and E dimensions of FMFM in BMMSC group were better than those of BMMNC group and control group (P< 0.05), and total scores of GMFM and FMFM were also better in the BMMSC group (P < 0.05). At 12 months after cell transplantation, scores in A, B and C dimensions of GMFM and A, B, C, D and E dimensions of FMFM scores in BMMSC group were all superior to those of BMMNC group and control group (P < 0.05) as well as the total GMFM and FMFM scores. There were six cases of low intracranial pressure headache in BMMNC group and six cases of low-grade fever in BMMSC group. In summary, both BMMSCs transplantation and BMMNCs transplantation are safe, effective and feasible for the treatment of spastic cerebral palsy in children, and moreover, BMMSCs transplantation is a better method than BMMNCs transplantation to improve gross and fine motor functions of spastic cerebral palsy children.

Objective: To summarize clinical experience on reconstruction of severe facial disfigurement with flap prefabrication and soft tissue expansion. Methods: From September 2005 to June 2016, 49 patients with type Ⅲ and type Ⅳ facial deformities underwent facial reconstruction with an integrated method on the basis of prefabricated flaps. In the first stage, the descending branch of the lateral femoral circumflex vessels and the surrounding muscle fascia were dissected and transferred to subcutaneous pocket in the cervicothoracic area. The pedicles of the fascial flap were anastomosed to either the facial or superior thyroid artery and their venae comitantes in flap prefabrication. A tissue expander was placed beneath the fascial flap. In the second stage, over-expansion was achieved with intra-flap stem cell transplantation once patient′s skin showed signs of intolerance to expansion. In the third stage, prefabricated flap was transferred to cover the facial defects. the second or third internal mammary artery perforators or lateral thoracic artery perforators were reserved and flap supercharging would be performed depending on the perfusion of the flap revealed by indocyanine green angiography intra-operatively. Later, flap revisions further restored facial outline and delicate organ configuration. Aesthetic and functional status were independently graded to assess the facial appearance and function before and after the reconstruction. Results: 49 patients with severe facial deformities were included. 5 patients received stem cell transplantation. The final inflated volume ranged from 2 530 ml to 3500 ml and each patient had facial reconstruction with a prefabricated flap (range 23 cm×18 cm-34 cm×32 cm). Flap supercharging technique were used in 25 cases to augment blood perfusion, however, flap necrosis (5 cm× 2 cm) occurred in 1 patient, and tip necrosis occurred in 4 patients, otherwise, all flaps survived entirely. The aesthetic (1.15 to 2.29) and functional (0.86 to 2.42) status scores were statistically improved (P<0.01). Facial expressions such as smiling, blinking and frowning were noted. Conclusions Autologous full face reconstruction with an integrated method based on flap prefabrication can bring satisfying aesthetic and functional recovery, rendering a safe and effective option for most patients with massive facial defects.