Therapeutic effects of shaogan fuzi decoction in rheumatoid arthritis: Network pharmacology and experimental validation.

Shaogan Fuzi Decoction (SGFD), one of the classical prescriptions of Chinese Medicine, has a long history in the treatment of rheumatoid arthritis (RA), but definitive studies on its efficacy and mechanism of action are lacking. This study aims to elucidate the pharmacodynamic role of SGFD against RA and the potential mechanisms based on a combination of network pharmacology and experimental verification. The RA model in rats was induced by intradermal injection of bovine type Ⅱ collagen and incomplete Freund's adjuvant at the tail root. SGFD was administered once a day by oral gavage for 4 weeks. After SGFD administration, rat's arthritis index (AI) score and paw swelling decreased to some extent, and synovial inflammation, vascular hyperplasia, and cartilage destruction of the ankle joint were improved. Simultaneously, thymus and spleen index and serum levels of C-reactive protein (CRP) were lowered. Network pharmacology revealed that quercetin, kaempferol, naringenin, formononetin isorhamnetin and licochalcone A were the potentialiy active components, and IL6, TP53, TNF, PTGS2, MAPK3 and IL-1ß were potential key targets for SGFD in the treatment of RA. Ingredients-targets molecular docking showed that the components had the high binding activity to these target proteins. The mechanism of SGFD for RA involves various biological functions and is closely correlated with TNF signaling pathway, Osteoclast differentiation, T cell receptor signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, NF-κB signaling pathway, toll-like receptor signaling pathway, and so on. Western blot and ELISA showed that the expression of toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB) p65, phosphorylated c-Jun N-terminal kinase (p-JNK), p-p38, phosphorylated extracellular regulated kinase (p-ERK) and TNF-α was significantly upregulated in the synovium of RA rats, and the levels of serum inflammatory factors were significantly increased. SGFD inhibits the activation of the TLR4/NF-κB/MAPK pathway and the expression/production of pro-inflammatory cytokines. In summary, SGFD could improve the symptoms and inflammatory response in collagen-induced arthritis (CIA) rat model. The mechanism might be related to the regulation of TLR4/MAPKs/NF-κB signaling pathway and the reduction of inflammatory factor release, which partially confirms the results predicted by network pharmacology.

Anatomical basis and clinical application of the dorsal perforator flap based on the palmar artery in the first web.

PURPOSE: Soft-tissue defects of the thumb and index finger remain a challenge for plastic surgeons. Our purpose was to observe the morphological characteristics of the cutaneous vessels in the first web, to design a dorsal perforator flap based on the palmar artery in the first web and to propose its clinical application. METHODS: Thirty preserved hand specimens were dissected to observe the origin, course, branch and anastomosis of the dorsal perforators in the first web, and the dorsal perforator flap based on the palmar artery in the first web was designed. Clinically, seven cases of hand defects were reconstructed using this flap. RESULTS: The blood supply for the dorsum of the first web comprised the dorsal perforators from both the dorsal artery (the branch of the first dorsal metacarpal artery) and palmar artery (the radial palmar digital artery of the index finger and the ulnar palmar digital artery of the thumb). The first dorsal metacarpal artery constantly arose from the radial artery and was divided into the radial, ulnar and medial branches. The palmar artery sent out 1-2 perforators and formed a constant anastomosis with the medial branch of the first dorsal metacarpal artery to supply the dorsal skin of the first web. In clinical application, all the flaps survived completely without contracture of the first web or other complications and the donor regions all healed at the first stage. CONCLUSION: The dorsal perforator flap based on the palmar artery in the first web is useful to repair soft-tissue defects of the thumb, the proximal phalanx of the index finger and thenar region, leading to a satisfactory appearance and good functional and sensory recovery.

Anatomical basis and design of the distally based lateral dorsal cutaneous neuro-lateral plantar venofasciocutaneous flap pedicled with the lateral plantar artery perforator of the fifth metatarsal bone: a cadaveric dissection.

BACKGROUND: Detailed investigation of the vasculature of the lateral aspect of the foot has rarely been presented. However, harvesting the flap in this area to cover defects of the foot and hand is highly important. Repair of soft-tissue defects at the forefoot remains a challenge in reconstructive surgery. This study explores the characteristics of the distal-based lateral dorsal cutaneous neuro-lateral plantar venofasciocutaneous flap pedicled with the lateral plantar artery perforator of the fifth metatarsal bone to establish a repair procedure for ulcers or defects in the forefoot region. METHODS: This study is divided into two parts: anatomical study and simulated operation. Thirty cadavers were utilized in the anatomical study after arterial injection. The tuberosity of the fifth metatarsal bone was used as the anatomical landmark. The lateral plantar artery perforator of the fifth metatarsal bone was identified through dissection. The perforators were dissected under a microscope. The details of the lateral plantar artery perforators, the distribution of the lateral dorsal cutaneous nerve and lateral plantar vein, the anastomosis in the lateral plantar artery perforator of the fifth metatarsal bone, the nutrient vessels of the lateral dorsal cutaneous nerve and lateral plantar vein, and other arteries of the lateral foot were recorded. The flap-raising procedure was performed on three fresh cadavers. RESULTS: The lateral dorsal cutaneous nerve originated from sural nerve, traveled obliquely downward along the anterior lateral margin of the foot, and accompanied by the lateral plantar vein after bifurcation, and was eventually distributed on the lateral aspect of the foot. The nutrifying arteries to the lateral dorsal cutaneous nerve and lateral plantar vein were present segmentally and mainly originated from the lateral plantar artery perforator of the fifth metatarsal bone. These nitrifying arteries constantly originated from the lateral plantar artery in the area of tuberosity of the fifth metatarsal, ran along the medial side of the fifth metatarsal, traveled between the fifth metatarsal bone and the lateral muscle group (the flexor digitorum brevis and the abductor digiti minimi muscles), pierced the aponeurosis, vascularized the skin of the anterior lateral plantar region, and resulted in many minute branches, which anastomosed with the lateral tarsal artery and fourth dorsal metatarsal artery. The anatomical study showed that (1) the vasculature pattern can roughly be classified into three types and (2) constant anastomoses occurred between the above-mentioned arteries in the lateral-dorsum region of the foot. CONCLUSION: A reliable large- or medium-sized neuro-venocutaneous flap with lateral dorsal cutaneous nerve, lateral plantar vein, and nutrient vessels can be raised using only the perforator of the lateral plantar artery of the fifth metatarsal bone, which is thin, is in the immediate vicinity of the forefoot, and has a reliable retrograde blood supply. This flap can be considered an alternative means to reconstruct soft-tissue defects of the forefoot.

Anatomic basis and clinical application of the distally based medialis pedis flaps.

BACKGROUND: Soft-tissue defects of the forefoot are difficult to cover adequately, particularly, although multiple options for reconstruction are available. This study especially focused on the vascularization of the medial side of the foot and the determination of the contribution of the nutrient vessels to medialis pedis flap viability. METHODS: Thirty cadavers were available for this anatomical study. Microdissection was conducted under a microscope, and details of the course and distribution and the communication of the first plantar metatarsal artery with the fascial vascular network of the medial side of the foot were recorded. Clinically, six cases of soft-tissue defects at the forefoot region were reconstructed with distally based medialis pedis flap. RESULTS: The perforator of the first plantar metatarsal artery pierces in the superficial fascia of the medial aspect of the foot 2.2 ± 0.7 cm proximal to the first metatarsophalangeal joint, vascularize the skin of the medial plantar region. The anatomical study showed that the vasculature pattern could roughly be classified into two types. In terms of clinical application, all flaps completely survived, and one patient had partial loss of skin graft. CONCLUSION: The perforators of the medialis pedis flap are presented constant. The forefoot region can be repaired by the distally based medialis pedis flap on the perforator of the medial plantar artery of the hallux or the first plantar metatarsal artery perforator with medial plantar vein, medial plantar cutaneous nerve and nutrient vessels.

Anatomic basis of the distally based venocutaneous flap on the medial plantar artery of the hallux with medial plantar vein and nutrient vessels: a cadaveric dissection.

PURPOSE: This study aims to identify a repair procedure for ulcers or defect of the forefoot region. The general distribution and variation of the vascular anatomy of the distally based venocutaneous flap on the medial plantar artery of the hallux with medial plantar vein and nutrient vessels were investigated. This study especially focused on the vascularization of the medial side of the foot and the determination of the contribution of the nutrient vessels of medial plantar vein and medial dorsal cutaneous nerve to flap viability. Experiments were conducted to obtain information for operating procedures and to understand the vascular reliability of the flap. METHODS: Thirty cadavers were available for this anatomical study after arterial injection. The tuberosity of the fifth metatarsal bone was adopted as the anatomical landmark. Microdissection was conducted under a microscope, and details of the course and distribution of the medial plantar vein and the communication of the medial plantar artery of the hallux with the fascial vascular network surrounding the medial plantar vein were recorded. The flap-raising procedure was performed in a fresh cadaver specimen. RESULTS: The medial plantar vein was incorporated by the medial end of the dorsal pedal vein arch and medial dorsal vein of the hallux around the first metatarsal-medial cuneiform joint. It traveled along the medial margin of the foot and drained into the great saphenous vein at the level of the medial malleolar. The outer diameter of the nerve at the intermalleolar line was 3.2 ± 0.5 mm. These nutrifying arteries to the medial plantar vein were present segmentally and mainly came from the medial plantar artery of the hallux, which traveled forward in the fascia between the abductor hallucis tendon and the first metatarsal bone, emerged into the superficial layer 2.2 ± 0.7 cm proximal to the first metatarsophalangeal joint, and gave off many minute branches. These branches communicated with the fascial vascular network surrounding the medial plantar vein, supplying the fascia and integument of the medial foot. CONCLUSION: Reliable venocutaneous flap with medial plantar vein and nutrient vessel flaps can be raised based solely on the perforator of the medial plantar artery of the hallux. This flap should be considered as a preferential way to reconstruct soft-tissue defects of the forefoot.