Objective To observe the intervention effect of acupuncture at"Zusanli"(ST36)or"Neiguan"(PC6)on the ulcerative colitis(UC)model mice.And to analyze the similarities and differences of gene transcription expression between the diseased colon and the non-diseased heart after acupuncture intervention by using transcriptomics,to explore whether there are efficacy differences between the two acupoints.Methods The UC mouse model was established by inducing dextran sulfate sodium salt(DSS).After successful modeling,the mice were randomly divided into model group,Zusanli group,and Neiguan group,with 9 mice in each group.Zusanli group and Neiguan group intervened with acupuncture at"Zusanli"and"Neiguan",respectively,30 min each time,once a day,for 5 consecutive days.The control and model groups were only bound without acupuncture.Observe the general situation of mice in each group,calculate the disease activity index(DAI),observe the morphological changes of colon tissue by HE staining.Use transcriptome sequencing technology to sequence and biologically analyze the colon tissue of mice in each group,and compare and study whether the two acupoints have differences in acupoint efficacy from the perspective of diseased tissue.At the same time,take the heart tissues of each group for comparative analysis,and discuss whether the effects of the two acupoints are different from the perspective of non-diseased tissue.Results Compared with control group,the DAI score of the model group increased significantly(P<0.001),and HE staining results showed significant pathological damage;after acupuncture at Zusanli or Neiguan,the DAI scores of UC mice were reduced considerably(P<0.05),and the pathological damage was significantly improved.The results of transcriptome sequencing and bioinformatics analysis showed that the effects of acupuncture at Zusanli or Neiguan on the colon of diseased tissue involved multiple genes,and 825 differential genes with similar changes(co-DEGs)were mainly enriched in white blood cells and chemokine pathways;there were 168 differentially expressed genes(ST36 only-DEGs)affected only by Zusanli,which were enriched to gastric acid secretion and other pathways;there were 325 differentially expressed genes(PC6 only-DEGs)only affected by Neiguan,which were enriched in cytokine-cytokine receptor interaction and other pathways.There were 95 co-DEGs in the heart of non-diseased tissue,which were mainly enriched in positive regulation of defense response and response to interleukin-1;there were 28 ST36 only-DEGs;there were114 PC6 only-DEGs,which were enriched in cardiovascular diseases and other pathways.Conclusion Acupuncture of"Zusanli"and"Neiguan"could improve UC mice's symptoms and pathological colon changes.However,through transcriptomic analysis,it was found that the two acupoints had differences in gene transcription effects on the colon of diseased tissue and the heart of non-diseased tissue,suggesting that acupoints with different distribution positions had some similarities in macro efficacy.Still,there were some differences at a micro level.

Objective To explore the effects of different acupoints,different target organs,and different interventions on acupoint efficacy based on ACU&MOX-DATA platform;To illustrate and visualize whether the above factors have the characteristics of"specific effect"or"common effect"of acupoint efficacy.Methods The multi-source heterogeneous data were integrated from the original omics data and public omics data.After standardization,differential gene analysis,disease pathology network analysis,and enrichment analysis were performed using Batch Search and Stimulation Mode modules in ACU&MOX-DATA platform under the conditions of different acupoints,different target organs,and different interventions.Results Under the same disease state and the same intervention,there were differences in effects among different acupoints;under the same disease state,the same acupoint and intervention,the responses produced by different target organs were not completely consistent;under the same disease state and acupoint,there were differences in effects among different intervention measures.Conclusion Based on the analysis of ACU&MOX-DATA platform,it is preliminary clear that acupoints,target organs,and interventions are the key factors affecting acupoint efficacy.Meanwhile,the above results have indicated that there are specific or common regulatory characteristics of acupoint efficacy.Applying ACU&MOX-DATA platform to analyze and visualize the critical scientific problems in the field of acupuncture and moxibustion can provide references for deepening acupoint cognition,guiding clinical acupoint selection,and improving clinical efficacy.

OBJECTIVE To analyze the types and control measures of major microorganisms in pharmaceutical water systems, so as to provide guidance for effective control of pharmaceutical water systems. METHODS The main microbial species, abundance and harmfulness of drinking water, purified water and water for injection were reviewed, and the control measures on microorganisms in pharmaceutical water were discussed. RESULTS There were differences in the main microbial types in pharmaceutical water. Burkholderia cepacia complex and Ralstonia pickettii were conditioned pathogens in pharmaceutical water, thus causing certain biological safety hazards. CONCLUSION Pharmaceutical companies can strengthen the control of microorganisms in the water system by establishing microbial databases and common microbial strain banks at all levels. Trend analysis should to be conducted based on alert limits and action limits, so as to strengthen the control of microorganisms in the water system.

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor

Chronic osteomyelitis is a serious clinical problem with repeated courses and high disability rate, which seriously affects the physical and mental health of patients. Through continuous learning and summary in the process of using traditional therapies, the innovative improvements and changes had made in the treatment of osteomyelitis: Radical debridement of lesions was performed by applying the basic principles of modern bone tumor surgery. The application of microsurgical technique to transfer composite tissue flap can provide guarantee for tissue defect repair and wound closure without tension. Combined with bone grafting, local antibiotics and bone fixation, an one-stage operation has significantly improve the therapeutic effect of chronic complex osteomyelitis.

Objective:To study the efficacy of different systemic chemotherapy regimens as first-line and second-line therapy and to determine the prognostic factors for patients with advanced biliary tract cancer.Methods:The clinical data of patients with advanced biliary tract cancer who underwent systemic chemotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2018 were studied. The efficacy of chemotherapy on objective response rate (ORR) and disease control rate (DCR) were evaluated. Potential prognostic factors for survival were studied using the Cox proportional hazards models.Results:Of 151 patients enrolled into this study, there were 75 males and 76 females, with ages ranging from 31 to 77 years (median 58 years). Two treatment protocols were used: (1) 104 patients received a gemcitabine-based regimen (combined with platinums or fluorouracils) or a combination of platinums and fluorouracils, while (2) 47 patients received a combination of albumin-bound paclitaxel and S-1. The corresponding ORR for each group were 15.4%(16/104) and 27.6%(13/47), respectively, and the DCR were 65.4%(68/104) and 72.3%(34/47), respectively. Of 58 evaluable patients who received chemotherapy as a second-line therapy, 31 patients received the regimen containing gemcitabine, platinums or fluorouracils with an ORR of 3.2% (1/31) and a DCR of 35.5%(11/31); a total of 18 patients received the taxanes-based regimen with an ORR of 11.1%(2/18) and a DCR of 38.9%(7/18); 9 patients received the irinotecan-based regimen with an ORR of 22.2%(2/9) and a DCR of 44.4%(4/9). Univariate analysis showed positive liver metastasis and elevated carbohydrate antigen (CA)19-9 level to be significantly correlated with worse survival outcomes ( HR=1.540, 95% CI: 1.019-2.328, P=0.040 and HR=1.892, 95% CI: 1.123-3.188, P=0.017). Conclusion:For patients with advanced biliary tract cancer, in addition to the conventional regimens containing gemcitabine, platinums and fluorouracils, the combination of albumin-bound paclitaxel and S-1 was shown to be an effective chemotherapeutic regimen for these patients. Second-line chemotherapy was insufficient and ineffective, and an irinotecan-based regimen deserves to be further investigated. Liver metastasis and elevated CA19-9 level were worse prognosis after chemotherapy for patients with advanced biliary tract cancer.

Objective:To investigate the clinical efficiency of gastrocnemius muscle flap combined with antibiotics loaded calcium sulfate in the treatment of postoperative infection and plate exposure of tibial plateau fracture in elderly patients.Methods:From January, 2015 to May, 2019, 21 elderly patients with postoperative infection and plate exposure of tibial plateau fracture were treated, including 14 males and 7 females with an average age of 72.6 years, ranging from 61 to 82 years. The average course of disease was 22.7 days, ranging from 6 to 91 days. The site of wound infection was at medial in 8 cases, lateral in 9 cases and bilateral in 4 cases. The size of wound ranged from 2.0 cm×3.5 cm to 5.0 cm×12.0 cm. All wounds were implanted with antibiotics loaded calcium sulfate and repaired by gastrocnemius muscle flap combined with skin graft after debridement. Muscle flap survival, wound healing, inflammatory index, fracture healing and knee joint function were recorded. The curative effect was evaluated by McKee infection treatment criteria and the knee joint function was evaluated by HSS scoring criteria.Results:All 21 muscle flaps survived. In 1 case, skin graft necrosis occurred in a small area, and the wound healed well after dressing change. One case had exudation which was clear and the bacterial culturing was negative, and the wound healed after 2 weeks of dressing change. The other incisions were healed in stage I, and the healing rate was 90%. All patients were followed-up for an average of 28.7(16-39) months. The redness and swelling occurred in 1 case without exudation after 2 months which disappeared after anti-infection treatment and didn't recur again. The infection recurred in 1 case after 5 months, and it which was controlled after debridement and plate removal. According to McKee criteria, 19 cases were cured, 1 improved and 1 recurred with an effective rate of 95.2%. The fracture healing time was from 3 to 7 months, with an average of 4.6 months. According to HSS scoring criteria, the knee joint function was excellent in 12 cases, good in 7 cases and moderate in 2 cases.Conclusion:After thorough debridement, gastrocnemius muscle flap combined with antibiotic loaded calcium sulfate can effectively control the infection, repair the wound, promote fracture union and restore limb function in the treatment of postoperative infection and plate exposure of tibial plateau fracture in elderly patients.

To investigate the effect and application value of transplantation of the free cutaneous fibular flap combined with antibiotic-loaded calcium sulfate artificial bone graft for the treatment of antibrachial chronic osteomyelitis of Cierny-Mader type IV. Methods From August, 2013 to May, 2017, 12 cases of ulna or (and) radius chronic osteomyelitis of Cierny-Mader type IV were treated by transplantation of the free cutaneous fibu-lar flap combined with antibiotic-loaded calcium sulfate artificial bone graft. There were 7 males and 5 females, with an average age of 36.3 (21-47) years.Pure ulnar osteomyelitis in 7 cases, radius osteomyelitis in 4 cases, and both ul-nar and radius osteomyelitis in 1 case. The average range of osteomyelitis lesions was 6.3 (3.0-9.0) cm. The area of soft tissue defect (including bone scar) ranged from 8.0 cm×2.0 cm to 15.0 cm×5.0 cm. The area of the flap was 10.0 cm×3.5cm-17.0 cm×7.0 cm.The average length of the fibular flap was 8.8 (5.0-12.0) cm.Locking plate internal fixa-tion was used in 9 cases, external fixator in 2 cases, and plate combined with external fixator in 1 case. Vancomycin/gentamicin, an effective component of calcium sulfate artificial bone, averaged 0.64 g/102.7 kU (0.4 g/64 kU-1.0 g/160 kU).Routine postoperative treatment.And monthly outpatient review in the first half year after operation, and outpatient review every 3 months after half a year.One year after operation, comprehensive evaluation of elbow, forearm and wrist function with Mayo Elbow Function Index, Anderson Forearm Double Fracture Evaluation System and Cooney Wrist Function Score. Results Vascular crisis occurred in 1 case after operation, prompt surgical exploration, and ultimately all flaps survived completely.The donor sites healed well in all cases.The lower extremity functions of donor sites had no change compared with that before operation.Followed-up of an average of 22.7 months, there were 2 cases who had sen-sory disturbance in the ulnar nerve innervation area and returned to normal 3 months after operation. The fibular flaps healed satisfactorily with an average healing time of 4.7 (3-6) months.No calcium sulphate artificial bone granules were seen on X-ray at 3 months after operation.One year after operation, bone healing, forearm appearance and wrist function recovered well, but elbow and forearm motor function recovered unsatisfactorily. Conclusion On the basis of master-ing the applied anatomy and vascular anastomosis techniques of microsurgery, this method of transplantation of the free cutaneous fibular flap combined with antibiotic-loaded calcium sulfate artificial bone graft for the treatment of an-tibrachial chronic osteomyelitis of Cierny-Mader type IV has achieved satisfactory results.The recipient area is beautiful. The bone healing is reliable.And it has little influence on the recipient area and the donor area.It is worthy of clinical application.

Objective To investigate the clinical efficacy of tissue flap combined with antibiotic-loaded calcium sulfate and autogenous iliac bone grafting at stage Ⅰ for infected nonunion of long bone.Methods A retrospective case series study was conducted to analyze the clinical data of 51 patients with infected nonunion of long bones admitted to Tongde Hospital of Zhejiang Province from January 2013 to December2017.There were 42 males and nine females,aged 19-71 years,with an average age of 36.3 years.There were 43 patients with bone nonunion at tibia,six at femur,one at humerus,and one at ulna and radius.The range of bone defect area was 1-9 cm,with an average of 2.9 cm.On the basis of thorough debridement,tissue flaps combined with antibiotic-loaded calcium sulfate and autologous iliac bone graft were performed at stage Ⅰ treatment.The survival of skin flaps,infection control,nonunion healing and complications were recorded.Johner-Wruhs joint function assessment criteria were used to evaluate limb function.Results All patients were followed up for 10-35 months,with an average of 18.3 months.All flaps survived eventually.Except for one patient with infection recurrence,the other 50 patients with infection obtained primary cure.All nonunions were healed,with an average healing time of 6.4 months ranging from 4 to 15 months.Complications included venous crisis of skin flaps in five patients,anterolateral femoral cutaneous nerve injury in 20 patients,recurrence of infection in one patient,and infection of external fixator nail tract in three patients.Function evaluation results by Johner-Wruhs criteria were excellent in 34 patients,good in 14,and moderate in three patients,with an excellent and good rate of 94％.Conclusion On the basis of thorough debridement,tissue flap combined with antibiotic-loaded calcium sulfate and autogenous iliac bone graft can control the infection effectively,promote the bone union and improve the limb function.

Objective To analysis causes of the serious complications after the operation of the lower leg perforator pedicle screw flap, and to explore the corresponding countermeasures. Methods From June, 2012 to Au-gust, 2016, 60 cases of soft tissue defect of ankle and foot were repaired with propeller flaps pedicled with perforator of lower legs. with the area were soft tissue defect ranged from 3.0 cm ×2.0 cm to 19.0 cm ×9.0 cm, and all with bone exposure. Two cases of traumatic tissue defect, 7 cases were chronic osteomyelitis of the distal tibia, 13 cases were in-cision infection and necrosis after the operation of ankle joint fracture and Pilon fracture, 10 cases were simple inci-sion necrosis after calcaneal fracture, 18 cases were calcaneal osteomyelitis, 1 case were soft tissue defect after the ankle tumor operation, 6 cases were soft tissue necrosis after the Achilles tendon rupture, and 3 cases were soft tissue defect of the dorsum with infection. The posterior tibial artery perforator pedicled propeller flap was used in 18 cases. The pedicle of the vascular pedicle was 6.0-18.0 cm from the medial malleolus, the flap rotation was 135 °-180° . There were 42 cases of the perforator pedicle propeller flap of the peroneal artery, 5.0-18.0 cm from the pedicle of the vascular pedicle and 120°-180° rotation in the flap. The area of the flap was 9.0 cm ×3.0 cm-34.0 cm ×18.0 cm. There were 32 cases of direct suture in the donor site and 28 cases of free skin grafting. Results The color, swelling, elasticity, capillary reaction and healing of donor site were observed after operation. There was no flap ischemia occurred in 60 patients. Fourteen cases had venous reflux obstruction, all of which had swelling above II degree, 8 cases had swelling above III degree with obvious purple blood stasis, resulting in partial flap necrosis in 4 cases, all necrosis in 1 case, including 4 cases of free skin grafting, 1 case of flap transplantation and repair. There were 3 cases of necrosis after skin grafting in the flap area, all of which were partial necrosis. There was case of necrosis of the wound surface after di-rect suture of the donor site and 1 case of skin disintegration after disassembly, and all wounds healed after the replace-ment of the wound and the external use of the dried blood powder. All the 60 patients were followed-up for 12 to 30 (mean, 24.5)months. The flaps survived and the donor site scars healed well. The range of motion of the ankle was from-10°to 10°(mean, 5.6 °) and the flexion of the plantar was from 20 °to 50 °(mean, 37.8 °). Fourteen patients with venous reflux disorder were followed up for 15 to 28(mean, 22.3)months. The flap and skin graft survived well. Ankle dorsiflexion ranged from-10° to 10 °(mean, 2.4 °) and plantar flexion from 20° to 45 °(mean, 35.6 °). There was no obvious limp in walking. Conclusion Although the overall effect of the lower leg perforator pedicle propeller flap to repair the soft tissue defect of the foot and ankle is satisfactory, there are still various serious complications, which are mainly due to ia-trogenic. Doctors should strictly follow the basic principles of skin flap surgery from preoperative to postoperative, and during operation and postoperative management, so as to reduce the incidence of complications.