An anatomical study of the tibial nerve branches innervating the posterior tibial artery.

The arteries of the lower limbs are innervated by vascular branches (VBs) originating from the lumbar sympathetic trunk and branches of the spinal nerve. Although lumbar sympathectomy is used to treat nonreconstructive critical lower limb ischemia (CLLI), it has limited long-term effects. In addition, the anatomical structure of tibial nerve (TN) VBs remain incompletely understood. This study aimed to clarify their anatomy and better inform the surgical approach for nonreconstructive CLLI. Thirty-six adult cadavers were dissected under surgical microscopy to observe the patterns and origin points of VBs under direct vision. The calves were anatomically divided into five equal segments, and the number of VB origin points found in each was expressed as a proportion of the total found in the whole calf. Immunofluorescence staining was used to identify the sympathetic nerve fibers of the VBs. Our results showed that the TN gave off 3-4 VBs to innervate the posterior tibial artery (PTA), and the distances between VBs origin points and the medial tibial condyle were: 24.7 ± 16.3 mm, 91.7 ± 66.1 mm, 199.6 ± 52.0 mm, 231.7 ± 38.5 mm, respectively. They were mainly located in the first (40.46%) and fourth (31.68%) calf segments, and immunofluorescence staining showed that they contained tyrosine hydroxylase-positive sympathetic nerve fibers. These findings indicate that the TN gives off VBs to innervate the PTA and that these contain sympathetic nerve fibers. Therefore, these VBs may need to be cut to surgically treat nonreconstructable CLLI.

Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway.

Fasudil is reported to be effective at protecting against ischaemic diseases, and at augmenting axon growth. In this study, we aim to evaluate its efficacy in promoting flap survival and reinnervation. Ninety-two Institute of Cancer Research (ICR) mice were used and divided into the control, Fasudil, LY294002, Fasudil+LY294002 groups, receiving a daily intraperitoneal injection of normal saline, Fasudil (10 mg/kg), LY294002 (5 mg/kg), and Fasudil (10 mg/kg) + LY294002 (5 mg/kg), respectively. On days 0 and 5, the blood perfusion and diameter of the iliolumbar artery in the pedicle of the flaps in the four groups were evaluated using laser speckling contrast imaging (LSCI). On day 5, the flaps were photographed and the necrosis rate of the flaps was calculated using Photoshop CS6. In addition, tissues were harvested from the flaps and divided into two parts. One part underwent routine cryosection and immunofluorescent staining using the antibody against CD31 for evaluation of the microvascular density in the four groups. In the other part, the expression of RhoA, ROCK1+2, p-CPI-17, p-MYPT, p-PTEN, p-PI3K, p-Akt, and vascular endothelial growth factor (VEGF) within the flaps were determined using western blotting. Moreover, at days 0, 7, 15, and 30 after flap surgery, the axons within the flaps were evaluated using immunofluorescent staining with the antibody against Neurofilament-200. It turned out that the necrosis rate was (24.4 ± 7.7)%, (5.2 ± 1.6)%, (29.8 ± 4.2)%, and (30.9 ± 7.1)%, respectively, in the control, Fasudil, LY294002, LY294002+Fasudil groups. There was a significant reduction in the necrosis rate of the flaps in the Fasudil group (P < .001). The LSCI and immunofluorescent staining demonstrated that Fasudil could significantly expand the diameter of the iliolumbar artery in the pedicle, boost the overall blood perfusion, and increase the microvascular density of the flaps in the Fasudil group (P < .05), which could all be abolished by PI3K inhibitor LY294002. On day 5, the expression of p-CPI-17, p-MYPT, and p-PTEN were downregulated, whereas pPI3K, p-Akt, and VEGF were upregulated in the Fasudil group (P < .001). As for reinnervation, Neurofilament-200 fluorescent staining revealed that at days 15 and 30 after flap harvest, only in the Fasudil group could new axons be observed. It can be concluded that Fasudil could simultaneously improve the survival and axon growth after flap harvest, a dual efficacy achieved by inhibition of the RhoA/ROCK pathway, which in turn activates /PI3K/AKT pathway.

Segmental branches emanating from saphenous nerve morphing into sympathetic trunks for innervation of saphenous artery and its clinical implication for arterial sympathectomy.

Sympathectomy of arteries has been adopted for the treatment of peripheral arterial disease and Raynaud's disease. However, the exact route for sympathetic axons to reach peripheral arteries awaits further investigation that could pave the way for development of new surgical strategies. In this study, saphenous neurovascular bundles from 10 neonatal Sprague-Dawley rats first were harvested for whole-mount immunostaining to show sympathetic innervation pattern of the artery. Secondly, 40 Sprague-Dawley male rats weighing 350 to 400 g were assigned to five groups, receiving either sham, perivascular sympathectomy, nerve-artery separation, nerve transection in the saphenous neurovascular bundle, or lumbar sympathectomy surgery that removes the lumbar sympathetic trunks. Immediately after surgery, the arterial perfusion and diameter were measured using laser speckling contrast imaging, and 1 week later the saphenous neurovascular bundles were harvested for immunostaining using antibodies against TH, neuron-specific ß-tubulin (Tuj 1), and α-SMA to show the presence or absence of the TH-immuopositive staining in the adventitia. The differences among the five groups were determined using one-way analysis of variance (ANOVA). We found that an average of 2.8 ± 0.8 branches with a diameter of 4.8 ± 1.2 µm derived from the saphenous nerve that morphed into a primary and a secondary sympathetic trunk for innervation of the saphenous artery. Nerve-artery separation, nerve transection, and lumbar sympathectomy could eradicate TH-immunopositive staining of the artery, resulting, respectively, in a 12%, 36%, and 59% increase in diameter (P < .05), and a 52%, 63%, and 201% increase in perfusion compared with sham surgery (P < .01). In contrast, perivascular sympathectomy did not have a significant impact on the TH-immunopositive staining, the diameter, and perfusion of the distal part of the artery (P > .05). We conclude that the sympathetic innervation of an artery derives from segmental branches given off from its accompanying nerve. Nerve-artery disconnection is a theoretic option in sympathectomy of an artery.

Mechanically Induced Vasospasm-Evaluation of Spasmolytic Efficacy of 10 Pharmaceutical Agents Using Laser Speckle Contrast Imaging.

BACKGROUND AND OBJECTIVES: Vasospasm is a thorny problem often encountered in microvascular surgery that seriously threatens the survival of vascularized tissue transfers. This investigation is dedicated to establishing a model of vasospasm and to evaluating the antispasmodic efficacy of 10 pharmacologic agents. STUDY DESIGN/MATERIALS AND METHODS: Eighty Sprague-Dawley rats were used. After anesthesia and depilation, the femoral neurovascular bundle was exposed, and a pair of microsurgical forceps were used to trigger vasospasm of the femoral vessels by blunt dissection. Then, 10 pharmacological agents, namely, prostaglandin E1, sodium nitroprusside, magnesium sulfate, papaverine, normal saline, phentolamine, verapamil, 2% lidocaine hydrochloride, amrinone, and 12% lidocaine hydrochloride, were dripped to the femoral vessels, after which laser speckle contrast imaging was used to collect perfusion images, acquiring the perfusion and the inner caliber of the femoral vessels at multiple timepoints. Furthermore, blood perfusion and the time consumed to escape vasospasm and reach hyperperfusion in each group were calculated. The difference of spasmolytic efficacy among the agents was statistically analyzed by one-way analysis of variance. RESULTS: There was a significant difference in antispasmodic ability among the 10 agents (P < 0.001). 10% magnesium sulfate and 12% lidocaine were distinguished among the 10 agents in resolving the vasospasm. 10% magnesium sulfate demonstrated the best antispasmodic potency, which enabled the shortest time consumed for vessels to escape spasm and reach hyperperfusion. 12% lidocaine ranked second in efficacy, demonstrating a similar effect except that it could not propel the femoral vein to a state of hyperperfusion. For the remaining agents, the time consumed for the artery to escape spasm was all significantly shortened when compared with normal saline (P < 0.001). For the venous spasm, all agents except prostaglandin E1 could significantly shorten the time consumed for the vein to escape spasm (P < 0.001). CONCLUSIONS: In terms of resolving mechanically induced vasospasm, 10% magnesium sulfate is the best antispasmodic, followed by 12% lidocaine. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Arterial Supercharging Is More Beneficial to Flap Survival Due to Quadruple Dilation of Venules.

BACKGROUND: "Choke vessels" are communicating conduits between adjacent perforasomes in the skin. Most researches focus mainly on the arterial aspect of the "choke vessels" and neglect the venous aspect, an imbalance needed to be addressed. MATERIALS AND METHODS: The study was divided into parts I, II, and III. Part I was for observation of the vascular morphological evolution in the choke zone after flap harvest in rats. Part II was for determination of the importance of the dilation of the arterial and venous components of "choke vessels" by preserving the iliolumbar artery (ILA group) or vein (ILV group). A laser Doppler flowmeter and a speckle flow imaging system were adopted for monitoring the hemodynamic impact caused by the different manipulation. Part III was for corroboration of part II by manipulation of other vessels. RESULTS: In part I, the arteries and veins between the iliolumbar and intercostal perforasomes underwent modest dilation, whereas the venules between the veins nearly quadrupled in diameter. In part II, flaps in the ILA group were much more intensive in blood perfusion than flaps in the ILV group. The flap necrosis rate was 0.31 ± 0.07 in the ILV group, being significantly larger than 0.10 ± 0.03 in the ILA group. Part III confirmed that venous superdrainage is less efficacious in reducing flap necrosis than arterial supercharging, in which the position of the additional artery was far more important than the diameter. CONCLUSIONS: The extensive dilation of the venous component of choke vessels makes a more potent compensatory role for venous drainage after flap harvest, indicating arterial supercharging is better in augmenting flap viability than venous superdrainage.

Quantification of axonal ingrowth and functional recovery in a myocutaneous flap model in rats with strong clinical implications.

The process of reinnervation, an important component of functional restoration after flap transfer, is understudied, making it necessary to carry out a further investigation for delineation of the exact timeline. Seventy-six Sprague-Dawley rats were used as the experimental animals. An anatomic study was first conducted to clarify the pattern of nerve distribution in the dorsal skin of 16 rats. Afterward, a myocutaneous flap was harvested on the right flanks of 40 rats, which were then assigned into seven time points. At each time point, skin samples were harvested and immunofluorescent staining was performed using α-Bungarotoxin, and antibodies against NF-200, p75, α-SMA, and TH. One-way analysis of variance was adopted for comparison of nerve density after surgery. For evaluation of functional return, cutaneous trunci muscle reflex (CTMr) test was performed on 10 additional rats, and the Chi-square test was used for comparison of reflex intensity among six time points after surgery. The outcomes revealed that the cutaneous branches from the intercostal nerves and the dorsothoracic nerve from the brachial plexus could be found entering the dorsal skin, distributed in the skin proper and the panniculus carnosus, respectively. After flap surgery, full spontaneous reinnervation of the skin proper and vessels within the flaps could be achieved at day 180. However, if the stumps of cutaneous branches of the intercostal nerves were damaged, the nerve density in the skin proper underwent a 2/3 decline. The panniculus carnosus in the cranial part had a much better reinnervation than that in the caudal part. The CTMr test showed that the flap could regain most of its sensate and motor activity. Our study shows that strong spontaneous reinnervation could be expected after flap surgery. The pattern of the original nerve distribution in both the recipient and donor sites may have a big impact on the reinnervation of the flap.

The Skin Bridge Is More Important as an Additional Venous Draining Route in a Perforator-Plus Flap.

BACKGROUND: The skin bridge in the perforator-plus flap is considered as an additional source for arterial input and venous drainage apart from the perforator. However, its exact role requires further elucidation. MATERIALS AND METHODS: Forty rats that underwent flap elevation with a size of 9 × 3 cm on the dorsum were evenly divided into a perforators-intact group with an intact vascular pedicle, an artery-deficient group with the artery ligated, a vein-deficient group with the vein ligated, and a perforators-deficient group with both vessels ligated. The blood perfusion was measured using a laser Doppler flowmeter. On the seventh day, the necrosis rate of the flaps was calculated and the diameter of vessels in the skin bridge was measured. RESULTS: The perfusion pattern was similar between the perforators-intact group and vein-deficient group, as well as between the perforators-deficient group and artery-deficient group. The blood perfusion was much more robust in the perforators-intact and vein-deficient groups. The necrosis rate in the perforators-deficient group (26 ± 1%) was not significantly different from that in the artery-deficient group (29 ± 1%), both of which was significantly larger than that in the perforator-intact (11 ± 3%) and vein-deficient groups (12 ± 4%) (P ˂ 0.001). The venous network of the skin base in the vein-deficient and perforators-deficient groups dilated dramatically, whereas the arterial network in the artery-deficient and perforators-deficient groups had a very modest expansion. CONCLUSIONS: The skin base in a perforator-plus flap is much more important as an additional route for vein drainage than for arterial input.

NRCMS capitation reform and effect evaluation in Pudong New Area of Shanghai.

The Rural Cooperative Medical Scheme (RCMS) had played an important role in guaranteeing the acquisition of basic medical healthcare of China's rural populations, being an innovative model of the medical insurance system for so many years here in China. Following the boom and bust of RCMS, the central government rebuilt the New Rural Cooperative Medical Scheme (NRCMS) in 2003 across the whole country. Shanghai, one of the developed cities in China, has developed its RCMS and NRCMS as an advanced and exemplary representative of Chinese rural health insurance. But in the past 10 years, its NRCMS has encountered such challenges as a spiral of medical expenditures and a decrease of insurance participants. Previous investigations showed that the capitation and general practitioner (GP) system had great effect on medical cost containment. Thus, the capitation reform combined with GP system reform of NRCMS, based on a system design, was implemented in Pudong New Area of Shanghai as of 1 August 2012. The aim of the current investigation was to present how the reform was designed and implemented, evaluating its effect by analyzing the data acquired from 12 months before and after the reform. This was an empirical study; we made a conceptual design of the reform to be implemented in Pudong New Area. Most data were derived from the institution-based surveys and supplemented by a questionnaire survey, qualitative interviews and policy document analysis. We found that most respondents held an optimistic attitude towards the reform. We employed a structure-process-outcome evaluation index system to evaluate the effect of the reform, finding that the growth rate of the insured population's total medical costs and NRCMS funds slowed down significantly after the reform; that the total medical expenditure of the insured rural population decreased by 3.60%; and that the total expenditure of NRCMS decreased by 3.99%. The capitation was found to help the medical staff build active cost control consciousness. Approximately 2.3% of the outpatients flowed to the primary hospitals from the secondary hospitals; and farmers' annual medical burden was relieved to a certain degree. Meanwhile, it did not affect farmers' utilization and benefits of healthcare. However, further reform still faces new challenges: The capitation reform should be well combined with the primary healthcare system to realize the "dual gatekeeper" of GPs; a variety of payment methods should be mixed on the basis of capitation to avoid possible mistakes by one single approach; and the supervision of medical institutions should be strengthened. A long-term follow-up study need to be carried out to evaluate the effects of the capitation reform so as to improve the design of the program. Copyright © 2015 John Wiley & Sons, Ltd.

Revisit of the anatomy of the distal perforator of the descending genicular artery and clinical application of its perforator "propeller" flap in the reconstruction of soft tissue defects around the knee.

PURPOSE: In this article,we revisited the anatomy of the distal perforator of the descending genicular artery (DGA) and report the clinical application of its perforator propeller flap in the reconstruction of soft tissue defects around the knee. METHODS: Forty fresh human lower limbs were dissected to redefine the anatomy of the branches of the DGA and their perforators and the anatomical landmarks for clinical applications. Five patients underwent "propeller" distal anteromedial thigh (AMT) flaps based on DGA perforators for the reconstruction of post-traumatic (n = 4) and post-oncologic (n = 1) soft tissue defects occurring near the knee with a size ranging from 4.8 cm × 6.2 cm to 10.5 cm × 18.2 cm. RESULTS: A constant cutaneous perforator of the osteoarticular branch (OAB) of the DGA was found in the distal AMT fossa with a mean caliber of 1.2 ± 0.4 mm. It arose 9.4 ± 3.1 cm distally to the origin of the OAB and 4.0 ± 0.4 cm above the knee joint. The size of the harvested flaps ranged from 6.0 cm × 7.1 cm to 11.0 cm × 20.1 cm. All the flaps healed uneventfully at a mean period of 7.4 months. All the patients regained full range motion of the knee-joint. CONCLUSION: Our study provided evidence of the vascular supply and the clinical application of the distal AMT flap based on a constant perforator arising from the OAB of the DGA. This flap may be a versatile alternative for the reconstruction of the defects around the knee because of its consistent vascular pedicle, pliability and thinness, adequate retrograde perfusion, and the possible direct suture of the donor site.

Anatomical basis of the reverse lateral plantar artery perforator flap design.

BACKGROUND: This study aims to explore the characteristics of the formation and topography of lateral plantar artery perforators to identify a repair procedure for defects in the forefoot region. METHODS: Thirty-three cadavers were available for this anatomical study. The tuberosity of the fifth metatarsal bone was adopted as the anatomical landmark. The details of the lateral plantar artery perforators and the anastomosis between the lateral plantar artery perforators and other arteries of lateral foot were recorded. RESULTS: The perforators from the base and head of the fifth metatarsal bone constantly originate from the lateral plantar artery in the area of tuberosity of the fifth metatarsal, run along the medial side of the fifth metatarsal, then travel between the fifth metatarsal bone and lateral muscle group, pierce the aponeurosis, vascularize the skin of the anterior lateral plantar region, and finally anastomose with the lateral tarsal artery and the fourth dorsal metatarsal artery. At the point of origin, the mean sizes of the perforator of the fifth metatarsal base and head were 1.3 ± 0.2 and 0.9 ± 0.3 mm (mean ± SEM), respectively. The pedicle lengths were 2.6 ± 0.3 and 3.8 ± 0.5 cm, indicating the possibility of a free perforator flap. CONCLUSION: The lateral plantar artery perforators are presented constant. The forefoot region can be repaired by the reverse perforator flap harvested pedicled with either the lateral plantar artery perforator from the base or head of the fifth metatarsal bone.

Combination of Doxycycline with Metronidazole Protects against Pyroptosis in Rats with Endometritis through the Modulation of TLR4/NF-κB Pathway.

BACKGROUND: Endometritis is a condition usually resulted from the bacterial infection of uterus, causing pelvic disease, sepsis, shock, uterine necrosis and even death if it is inappropriately treated. The aim of this study is to explore the pathogenesis of endometritis, and investigate whether the combination of doxycycline and metronidazole offers stronger protection against lipopolysaccharide (LPS)-induced endometritis, and decipher more about the mechanisms underlying endometritis-related pyroptosis. METHODS: Sprague-Dawley (SD) rats were divided into five groups (n = 8 per group): control, model, metronidazole, doxycycline, and combination groups. In control group, the rats were injected with saline, while in other groups, lipopolysaccharide was injected into uterus of the rats to establish endometritis. Hematoxylin-eosin (H&E) staining was performed as part of the histopathological examination of endometrium. The integrity of chromatin and pyroptosis were evaluated by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay. Western blot and quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) were performed to ascertain the activation of toll-like receptors (TLR4)/nuclear factor-kappa B (NF-κB) pathway by detecting protein levels of phosphorylated p50 (p-p50)/p50, phosphorylated nuclear factor-kappa B (p-NF-κB)/NF-κB, phosphorylated IkappaB (p-IκB), and TLR4 protein and mRNA. Development of pyroptosis was also detected by determining the levels of caspase-1 and caspase-5 through Western blot and qRT-PCR. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of interleukin (IL)-1ß, IL-18, IL-2, IL-4, IL-6 and tumor necrosis factor alpha (TNF-α), and flow cytometry was adopted to determine T-helper (Th)1 and Th2 cell percentage to assess the extent of pyroptosis and Th1/Th2 imbalance. RESULTS: The uterine of the model group exhibited pathological alterations and higher degree of cell apoptosis. Compared with the control rats, model group showed lower protein levels of p-p50/p50 (p < 0.001), p-NF-κB/NF-κB (p < 0.001), p-IκB (p < 0.001), and TLR4 protein (p < 0.001) and mRNA (p < 0.001). Elevated levels of caspase-1 (p < 0.001), caspase-5 (p < 0.001), IL-1ß (p < 0.001), IL-18 (p < 0.001), IL-2 (p < 0.01), TNF-α (p < 0.05) and Th1/Th2 (p < 0.001) as well as reduced levels of IL-4 (p < 0.05) and IL-6 (p < 0.01) were observed in the model group, which could however be reversed by metronidazole (p < 0.01) or doxycycline (p < 0.01), with a more significant effect detected if a combination of the two drugs was administered (p < 0.01). CONCLUSIONS: The combination of doxycycline and metronidazole protects against rat endometritis by inhibiting TLR4/NF-κB pathway-mediated inflammation and suppressing pyroptosis.

Enhanced axon outgrowth of spinal motor neurons in co-culturing with dorsal root ganglions antagonizes the growth inhibitory environment.

Introduction: Forming a bridge made of functional axons to span the lesion is essential to reconstruct the motor circuitry following spinal cord injury (SCI). Dorsal root ganglion (DRG) axons are robust in axon growth and have been proved to facilitate the growth of cortical neurons in a process of axon-facilitated axon regeneration. However, whether DRG transplantation affects the axon outgrowth of spinal motor neurons (SMNs) that play crucial roles in motor circuitry remains unclear. Methods: We investigated the axonal growth patterns of co-cultured DRGs and SMN aggregates (SMNAs) taking advantage of a well-designed 3D-printed in vitro system. Chondroitin sulphate proteoglycans (CSPG) induced inhibitory matrix was introduced to imitate the inhibitory environment following SCI. Axonal lengths of DRG, SMNA or DRG & SMNA cultured on the permissive or CSPG induced inhibitory matrix were measured and compared. Results: Our results indicated that under the guidance of full axonal connection generated from two opposing populations of DRGs, SMNA axons were growth-enhanced and elongated along the DRG axon bridge to distances that they could not otherwise reach. Quantitatively, the co-culture increased the SMNA axonal length by 32.1 %. Moreover, the CSPG matrix reduced the axonal length of DRGs and SMNAs by 46.2 % and 17.7 %, respectively. This inhibitory effect was antagonized by the co-culture of DRGs and SMNAs. Especially for SMNAs, they extended the axons across the CSPG-coating matrix, reached the lengths close to those of SMNAs cultured on the permissive matrix alone. Conclusions: This study deepens our understanding of axon-facilitated reconstruction of the motor circuitry. Moreover, the results support SCI treatment utilizing the enhanced outgrowth of axons to restore functional connectivity in SCI patients.

The posterolateral mid-forearm perforator flap: anatomical study and clinical application.

BACKGROUND: Defects sustained at the distal forearm are common and pedicled perforator flaps have unique advantages in resurfacing it. The purpose of this study is to reappraise the anatomy of the perforator in the posterolateral aspect of the mid-forearm and present our clinical experience on using perforator flaps based on it for reconstruction of defects in the distal forearm. METHODS: This study was divided into anatomical study and clinical application. In the anatomical study, 30 preserved upper limbs were used. Clinically, 11 patients with defects at the forearm underwent reconstruction with the posterolateral mid-forearm perforator flaps. The defects, ranging from 4.5 × 2.5 cm to 10.5 × 4.5 cm, were located at the dorsal aspect of the distal forearm in 6 cases and at the volar aspect of the distal forearm in 5 cases. RESULTS: Three patterns of the perforator were observed in the posterolateral aspect of the mid-forearm, which originated from the posterior interosseous artery, the proximal segment of the radial artery or the radial recurrent artery, and the middle segment of the radial artery, respectively. The perforator was located 11.8 ± 0.2 cm to 15.8 ± 0.4 cm inferior to the lateral humeral epicondyle. Clinically, flaps in 8 cases survived uneventfully, while the other 3 cases suffered mild marginal epidermal necrosis, which was cured with continuous dress changing. CONCLUSION: The location of the perforator at the posterolateral aspect of the mid-forearm is consistent; the posterolateral mid-forearm perforator flap is particularly suitable to cover defects in the distal one-third of the forearm.

Matrix metalloproteinase-8 inactivates macrophage inflammatory protein-1 alpha to reduce acute lung inflammation and injury in mice.

To determine the role of matrix metalloproteinase-8 (MMP-8) in acute lung injury (ALI), we delivered LPS or bleomycin by the intratracheal route to MMP-8(-/-) mice versus wild-type (WT) mice or subjected the mice to hyperoxia (95% O(2)) and measured lung inflammation and injury at intervals. MMP-8(-/-) mice with ALI had greater increases in lung polymorphonuclear neutrophils (PMNs) and macrophage counts, measures of alveolar capillary barrier injury, lung elastance, and mortality than WT mice with ALI. Bronchoalveolar lavage fluid (BALF) from LPS-treated MMP-8(-/-) mice had more MIP-1alpha than BALF from LPS-treated WT mice, but similar levels of other pro- and anti-inflammatory mediators. MIP-1alpha(-/-) mice with ALI had less acute lung inflammation and injury than WT mice with ALI, confirming that MIP-1alpha promotes acute lung inflammation and injury in mice. Genetically deleting MIP-1alpha in MMP-8(-/-) mice reduced the increased lung inflammation and injury and mortality in MMP-8(-/-) mice with ALI. Soluble MMP-8 cleaved and inactivated MIP-1alpha in vitro, but membrane-bound MMP-8 on activated PMNs had greater MIP-1alpha-degrading activity than soluble MMP-8. High levels of membrane-bound MMP-8 were detected on lung PMNs from LPS-treated WT mice, but soluble, active MMP-8 was not detected in BALF samples. Thus, MMP-8 has novel roles in restraining lung inflammation and in limiting alveolar capillary barrier injury during ALI in mice by inactivating MIP-1alpha. In addition, membrane-bound MMP-8 on activated lung PMNs is likely to be the key bioactive form of the enzyme that limits lung inflammation and alveolar capillary barrier injury during ALI.

Penehyclidine enhances the efficacy of tropisetron in prevention of PONV following gynecological laparoscopic surgery.

PURPOSE: Postoperative nausea and vomiting (PONV) are common complications after gynecological laparoscopic surgery. Because monotherapy with antiemetics is insufficient, combinations of various antiemetics are often recommended by experts. In this study, our purpose was to find out whether penehyclidine could enhance the efficacy of tropisetron in preventing PONV. METHODS: With hospital ethics committee approval, we investigated 120 women undergoing gynecological laparoscopic surgery receiving prophylactic tropisetron (0.1 mg/kg; maximal dose, 5 mg) (group T) or tropisetron (0.1 mg/kg; maximal dose, 5 mg) plus penehyclidine (0.01 mg/kg; maximal dose, 1 mg) (group TP), or penehyclidine (0.01 mg/kg; maximal dose, 1 mg) (group P). The incidence of vomiting, the intensity of nausea (assessed by a visual analogue scale [VAS]), antiemetic rescues, and adverse effects were recorded at 2, 6, 12, and 24 h after surgery in the gynecological ward by a visiting nurse anesthetist who was unaware of the treatments. Collected data were analyzed using analysis of variance (ANOVA) and the χ(2) test. Continuous variables were expressed as means ± SD, and non-continuous variables were expressed as n (%). RESULTS: The overall incidence of vomiting was 28.3 % (34/120) in our study. The incidence of vomiting was significantly lower in group TP (4 cases, 10 %) than that in group T (12 cases, 30 %) and group P (18 cases, 45 %). The incidence of vomiting in group TP was also significantly lower than that in group T at 0-2 h and 2-6 h postoperatively and it was also significantly lower than that in group P at 0-2 h, 2-6 h, 6-12 h, and 12-24 h postoperatively. The incidence of vomiting was significantly lower in group T than that in group P at 12-24 h postoperatively. The VAS of nausea was significantly lower in group TP than that in group T and group P at 2 and 6 h after surgery. It also showed a significant higher score in group P than that at group T and group TP at 12 and 24 h. Within group P, the VAS of nausea was significantly lower at 2 h postoperatively than that at 24 h. CONCLUSIONS: Penehyclidine showed less efficacy in preventing PONV than tropisetron; however, compared with tropisetron or penehyclidine monotherapy, prophylactic medication with tropisetron plus penehyclidine significantly reduced the incidence of vomiting and decreased the intensity of nausea in women undergoing gynecological laparoscopic surgery.

Impact of Diameter of Perforator in Pedicle and Different Managements of Intermediate Non-Pedicle Perforator on Flap Survival in Rats.

BACKGROUNDS: The quantified relationship between perforator diameter and flap length can be supported, and the impact of different strategies of managements of a non-pedicled perforator with two major subfascial divisions on flap survival has never been explored. MATERIALS AND METHODS: This study was divided into two parts. In Part I, 48 Sprague-Dawley rats underwent flap harvesting based on six perforators with a diameter gradient. Then, the flap length and perforator diameter were measured for establishment of an equation. In Part II, 32 rats underwent harvest of a transverse flap based on the right superficial epigastric perforator. In 16 rats the right intermediate iliolumbar perforator was severed in a distal-to-division approach, whereas, in the other 16 rats, it was severed with in a proximal-to-division approach. Necrosis rates and blood perfusion were also compared. RESULTS: The equation y = 13.02 × x + 2.29 could be established between the perforator diameter in the pedicle (x) and the flap length (y) that could be supported with R2=0.8963 and P < 0.001.The transverse flap with a distal-to-division management of the intermediate iliolumbar perforasome was weaker in perfusion and had a necrosis rate of 49±4%, whereas the flap with a proximal-to division management had a significantly stronger perfusion and a lower necrosis rate of 21±2% (P<0.001). CONCLUSIONS: The safe flap length that can be estimated based on a perforator with a known diameter can be calculated using y=13.02× x +2.29. A short segment of the stem of an intermediate perforator with two major subfascial branches should be preserved to augment flap survival.

What should the government do regarding health policy-making to develop community health care in Shanghai?

BACKGROUND: The traditional three-stratum healthcare system, within which municipal, district and community hospitals all paid great attention to improving medical treatment service by developing medical technology, is no longer able to meet the current health needs in Shanghai. In 1997, the Chinese government called for the development of community health services to serve as a basic platform to provide public health service and basic medical cure. However, because the market-oriented economic reform was based on a fee-for-service mechanism (without a strict monitoring system), most community health centers (CHCs) still put great effort into developing medical services geared to profit, rather than to provide proper medical service for all and a "quality" public health service. To try to solve the problem, some government-controlled payment (GCP) system has been implemented in CHCs gradually in districts of Shanghai. The study intended to evaluate the impact of GCP solutions already implemented, as well as the impact of the standardized GCP system with supplementary solutions, in enabling CHCs to focus on providing quality public health services and appropriate medical treatment, rather than focusing on profit and loss, in order to meet the health needs aroused by major socioeconomic transition in Shanghai. METHOD: In order to make a systematic assessment, a standardized form of GCP was piloted for 6 months in Changning, Zhabei, and Songjiang districts, representing rich urban, poor urban and rich rural districts, respectively. We employed an evaluation index system with 26 indicators, based on a systematic review of literature and two rounds of Delphi consultation. The evaluation index system investigates four main themes of the reform: the government's role, the reform measures, the performance of CHC services and satisfaction with CHC services. We conducted an evaluation of the impact of both various types of GCP implemented in recent years and the standardized GCP system used during the more recent pilot project conducted across districts with different socioeconomic profiles. Cross-sectional comparisons between the pilot districts and control districts with similar socioeconomic context were also carried out to observe further the impact of the GCP system. RESULT: Various GCP systems were implemented in 2006 in Changning and Songjiang district and in 2007 in Zhabei district. These GCP systems were standardized in April 2009 and piloted for 6 months on this new basis in these three districts (Changning, Songjiang and Zhabei). The overall "outcome" scores based on an evaluation index applied to Changning, Zhabei, and Songjiang districts have been generally improving from 2004 to 2009. The improvements in outcome were significant after the districts had implemented various GCP solutions and increased further, albeit to a lesser extent, in the three pilot districts from April 2009 to September 2009, when the GCP systems were standardized by the implementation of some supplementary solutions. Cross-sectional comparisons between the pilot districts and control districts also indicated that CHC performance was consistently better in the pilot districts after the pilot period than in that of some other "control" districts. CONCLUSION: Although there have been other policies interacting with the impact of GCP, GCP reforms implemented in the pilot districts at different times (as well as the later, standardized GCP system) have been effective in enabling CHCs to focus on providing quality public health services and appropriate medical treatment, rather than concentrating upon profit and loss. The impact of the standardized GCP system was further confirmed by cross-sectional comparisons of some broad indicators, in terms of medical cost, quality of medical service, and coverage of public health service, between the pilot districts and control districts. However, uncertainties exit when looking at individual indicators. Some indicators (see pp. 11-13 and Table 5), such as the service contracting rate with CHCs and the proportion of residents with health records set up, were not sufficient to allow for reasonable estimation of the impact of the GCP. In part this was due to inconsistent data collections. Some indicators, on the other hand, such as the standard management rate of residents with hypertension, were usually affected by the changing government's role over the period. Meanwhile, variations among the three pilot districts with different socioeconomic profiles were observed by several individual indicators within the evaluation index. Further research is needed to investigate the impact of other solutions--such as user fee removal and "zero margin profit" of medicine in CHCs--in order to coordinate other policies with the GCP to improve CHCs more effectively. Longer term observation of impact of the standardized GCP system, as well as other influencing factors in Shanghai based on quality data collected on a standard basis, may help improve policy. Moreover, variations in residents' expectations of barriers in access to CHC services and in healthcare-seeking behavior need to be taken into consideration when designing GCP systems for areas with different socioeconomic profiles in order to meet the different health needs which are a consequence of the major socioeconomic changes in Shanghai (and China in general, it could be agreed).

High Levels of BMP2 Promote Liver Cancer Growth via the Activation of Myeloid-Derived Suppressor Cells.

Bone morphogenetic protein 2 (BMP2) signaling had significant roles in diverse pathological processes, such as cancer. Nevertheless, the interaction between BMP2 and carcinoma development remained largely unknown. In particular, the roles that BMP2 play in the development of liver cancer remained controversial, and mechanisms were unclear. BMP2 with strong osteogenic potential had been manufactured into various bone materials. However, cancer risk concerns were raised in recent years. Thus, we focused on analyzing the effects of exogenous BMP2 on the growth of liver cancer and the detailed mechanisms. We found that both intravenous injection of rhBMP2 and in vivo implantation of rhBMP2 materials could lead to the expansion of myeloid-derived suppressor cells (MDSCs) in peripheral blood and subsequently enhanced the infiltration of MDSCs into tumor in vivo. Furthermore, BMP2 signaling-activated MDSCs could secrete IL6 to enhance cell proliferation of liver cancer cells in vitro and facilitate liver cancer growth in vivo. Our study indicated that increased concentration of BMP2 within the peripheral blood could enhance liver cancer growth via the activation of MDSCs. In this study, the roles that BMP2 played in liver cancer growth were further confirmed and the detailed mechanisms about how BMP2 enhanced liver cancer growth were also elucidated.

Hemodynamic Study of Three Patterns of Flaps on Rats with a Novel Panoramic Photographing Technique Involved.

BACKGROUND: No study heretofore has been conducted to investigate the hemodynamic characteristics of the perforator, perforator-plus, and random flaps on an animal model. METHODS: Thirty Sprague-Dawley rats were equally divided into three groups: the perforator group, the perforator-plus group, and the random group. Laser Doppler flowmetry was adopted for measurement of blood perfusion of the flaps at six time points. Another nine rats were equally divided into three groups and underwent the corresponding surgery. On day 7, the flaps were photographed for calculation of the necrosis rate. The vascular network of flaps in each group was photographed immediately postoperatively and at days 3 and 7 after surgery with a special technique first proposed by us. RESULTS: No significant difference in flap necrosis could be detected in the perforator and perforator-plus flaps. Other than on day 1, when perfusion of the perforator was significantly stronger than that of the perforator-plus flap, there was no significant difference between the perforator and perforator-plus flaps. The three perforasomes in the perforator and perforator-plus flaps could all survive because of considerable dilation of vessels. On day 7, the vascular network between the iliolumbar perforator and the sacrococcygeal perforators underwent tremendous enlargement in diameter in the random flap group. CONCLUSIONS: The perforator flap and the perforator-plus flap are equal in blood perfusion. The survival of the random flap depends on the dilation of the vascular network between the pedicle and the nearest potential perforator.