WHO Guideline on Country Pharmaceutical Pricing Policies,published in 2020,outlines 10 commonly used pricing methods internationally.However,due to the unique composition of costs for traditional Chinese medicine(TCM),directly applying pricing methods designed for chemical and biological drugs may lead to discrepancies.Currently,in China,drug pricing primarily in-volves internal reference pricing,tender negotiation pricing,promoting the use of quality-assured generic and biosimilar drugs,and centralized procurement.It systematically analyzes various pricing methods and identifies their applicability and underlying reasons concerning the pricing of TCMwithin the medical insurance system.The method of value-based pricing and increasing price transparency has advantages for the pricing regulation of traditional Chinese medicine under medical insurance.

Adult ; Connexin 43 ; genetics ; Erythrokeratodermia Variabilis ; genetics ; Female ; Heterozygote ; Humans ; Male ; Mutation ; genetics ; Mutation, Missense ; genetics ; Pedigree

Wuxistatin, a novel and potent statin, is converted from lovastatin by Amycolatopsis sp. CGMCC1149. In the bioconversion, lovastatin is firstly hydroxylated by a hydroxylase. To obtain the critical hydroxylase, a novel hydroxylase gene was isolated from Amycolatopsis sp. CGMCC1149 by Degenerate PCR and Self-Formed Adaptor PCR and expressed in Escherichia coli. BLAST sequence analysis revealed that the gene belonged to cytochrome P450 gene superfamily and could encode a 403-amino-acid protein with a molecular weight of 44.8 kDa. The secondary structure prediction result showed that this protein contained many typical functional regions of P450, such as oxygen binding site, ion-pair region and heme binding region. Meanwhile, a catalytic function verification system was constructed by NADH, ferredoxin and ferredoxin reductase which could catalyze lovastatin hydroxylation into the target product. These would be helpful for further studies in large-scale production of wuxistatin.
Actinomycetales ; enzymology ; genetics ; Amino Acid Sequence ; Butyrates ; metabolism ; Cloning, Molecular ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Hydroxylation ; Industrial Microbiology ; Lovastatin ; metabolism ; Molecular Sequence Data

2,3-butanediol (2,3-BD) is a major byproduct of 1,3-propandediol (1,3-PDO) fermentation by Klebsiella pneumoniae. To decrease the formation of 2,3-BD, the budC and budA gene, coding two key enzymes of 2,3-BD synthetic pathway in K. pneumoniae, were knocked out using Red recombination technology. The growth of the two mutants were suppressed in different level. The budC deficient strain fermentation results showed that 1,3-PDO concentration increased to 110% and 2,3-butanediol concentration dropped to 70% of the parent strain. However, the budA deficient strain did not produce 1,3-PDO and 2,3-BD, and the final titer of lactic acid, succinic acid, ethanol and acetic acid increased remarkably compared with the parent strain. Further analysis of budC deficient strain fermentation inferred that K. pneumoniae possessed the 2,3-BD cycle as a replenishment pathway. The consequence provided a new evidence for reforming low-byproduct K. pneumoniae.
Acetolactate Synthase ; genetics ; metabolism ; Bacterial Proteins ; genetics ; Butylene Glycols ; metabolism ; Carboxy-Lyases ; genetics ; Gene Knockout Techniques ; Glycerol ; metabolism ; Klebsiella pneumoniae ; genetics ; metabolism ; Mutation ; Propylene Glycols ; metabolism

BACKGROUNDNeuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT). Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood.

METHODSWe used the rat chronic constriction injury (CCI) model for research, and degraded SNAP-25 by a single intrathecal administration of BoNT/A. The mechanical (MWT) and thermal withdrawal latency (TWL) were tested. The level of SNAP-25, GLT, and GAT-1 were assayed using RT-PCR and Western blotting.

RESULTSSNAP-25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP- 25 was correlated with the relief of nociceptive responses in CCI rats. MWT and TWL returned to normal from the 5th to 14th day (P < 0.05) after the administration. On the 14th day after surgery, compared to the sham group, the upregulation of SNAP-25 in CCI rats was reversed after BoNT/A treatment (P < 0.05). The decreased GLT was reversed after BoNT/A treatment but increased GAT-1 was not influenced by BoNT/A treatment.

CONCLUSIONSSNAP-25 and GLT play important roles in the development of neuropathic pain, and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury. Intrathecal administration of BoNT/A reversed the upregulation of SNAP-25 and downregulation of GLT after CCI, but had no significant effect on the expression of GAT-1.

Amino Acid Transport System X-AG ; genetics ; metabolism ; Animals ; Disease Models, Animal ; GABA Plasma Membrane Transport Proteins ; Male ; Neuralgia ; genetics ; metabolism ; Neuroglia ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Synaptic Transmission ; genetics ; physiology ; Synaptosomal-Associated Protein 25 ; genetics ; metabolism

Objective The study is to explore the extent, main-point and use of en bloc principle in re-operation of thyroid carcinoma. Methods Clinical data of 75 patients received re-operation from 2002 to 2006 because of nonstandard operation were reviewed, including 10 men, 65 women, age ranging from 21-56. lpailateral completing lobectumy, isthmectomy, ipsilateral anterior cervical muscle, and level Ⅵ dissetion were done in all the patients by en bloc principle. Results Residual tumor was found in 39 cases. There were, 10 in primary site, 8 in Ⅵ level, and 21 in beth. Therefore tumor residual rate was 52.0%. The total metastatic lymph nodes in Ⅵ level were 63. Among the eight patients with recurrent laryngeal nerves paralyses which were hurt in the first operation, 4 were found been cut completely, 4 were ligated. The ligated locations were all near the place which the nerve enter the larynx. The ligated nerves were released, and the patients voice was improved greatly. Conclusions Ipsilateral completing Iobectomy, isthmectomy, ipsilateral anterior cervical muscle and Ⅵ level dissetion is adequate for thyroid carcinoma patients who received nonstandard operation. The principle of en bloc resection can be used in the reoperation of thyroid carcinoma.

BACKGROUNDIn patients suffering from acute pancreatitis, the pathogenesis is not completely understood, and several recent studies in vitro suggested that heat shock proteins might play an important role in cell signaling. To investigate the possible role of extracellular heat shock protein 70 (Hsp70) in pancreatitis, toll-like receptor-4 (TLR4)-deficient and wild-type mice were administered with exogenous Hsp70 during the course of cerulein-induced pancreatitis (CIP).

METHODSAcute pancreatitis was induced by 5 intraperitoneal injections of cerulein at hourly intervals, and then treated with recombinant Hsp70 through the caudal vein 4 hours after the start of cerulein injections. Subsequently serum amylase and serum cytokines levels were detected. Histologic alteration of the pancreas was evaluated. Tumor necrosis factor alpha (TNF-alpha) concentrations and myeloperoxidase (MPO) activity in both pancreas and lungs were analyzed. The nuclear factor kappa B (NF-kappaB) activation in pancreatic tissue was measured using a sensitive RelA enzyme-linked immunosorbent assay.

RESULTSTreatment with recombinant Hsp70 to wild-type mice in CIP resulted in significant aggravation of inflammation in pancreas, elevated levels of serum cytokines, up-regulation of pulmonary MPO activity and increase of lung tissues TNF-alpha concentrations. In contrast, treatment with Hsp70 to TLR4-deficient mice had little effect on serum cytokines levels, pancreatic inflammation, pulmonary MPO activity and TNF-alpha concentrations.

CONCLUSIONSThe results suggest that extracellular Hsp70 might induce systemic inflammatory response syndrome (SIRS)-like response in vivo and TLR4 might be involved in the Hsp70-mediated activation of inflammatory reaction in the progression of CIP without infection.

Acute Disease ; Animals ; Ceruletide ; toxicity ; Female ; HSP70 Heat-Shock Proteins ; physiology ; Male ; Mice ; Mice, Inbred C57BL ; Pancreatitis ; etiology ; Systemic Inflammatory Response Syndrome ; etiology ; Toll-Like Receptor 4 ; physiology

OBJECTIVETo evaluate the patients with bone injury in Wenchuan earthquake.

METHODSFrom May 12th to June 15th 2008 the data of 1410 patients with bone injury in Wenchuan earthquake were analyzed to evaluate clinical intervention and remedy-managing experience.

RESULTSThe 1410 patients average age was from 4 to 103 years old. And 744 cases (52.7%) suffered from blunt injuries, 379 cases (26.9%) from buried injuries, 287 cases (20.4%) from falling injuries; And 1317 cases were with fracture, 93 with limbs soft tissue injuries; 261 patients combined with other parts of injuries including 45 cases with paralysis; 66 cases were with crush syndrome, 25 with gas gangrene, 76 with acute kidney failure, 26 with multiple organ failure. And 912 operations were performed including 402 fracture fixation, 224 debridement, 152 debridement and suture, 85 amputation, 29 implant skin, 8 fixation of joint dislocation, 5 surgical flaps transplantation, 4 nerve and tendon suture, 2 arthroscopes, 1 joint replacement. Among the 66 crush syndrome patients, 49 accepted continuous renal replacement therapy, in which 9 cases were bleeding from named arteries and 20 blood vessels were getting embolism. Among the 1410 cases, 1 died from multiple organ failure.

CONCLUSIONSAmong the patients with bone injury in Wenchuan earthquake, the elderly patients are more than the youth; The injuries are always combined with other complications; Opened injuries are polluted severely; It is difficult to deal with the crush syndrome; Paraplegia cases are less, but the amputees are more.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Earthquakes ; Female ; First Aid ; Humans ; Male ; Retrospective Studies ; Wounds and Injuries ; surgery

OBJECTIVETo investigate the clinical manifestations and risk factors of the patients from developmental dysplasia of the hip(DDH) family.

METHODSDetailed epidemiology investigation, physical examination, functional movement assessment, lab test and X-ray examination were applied to the whole members of a DDH family.

RESULTSIn the family with 9 generations and 218 persons, the incidence of DDH was 31.03% in 145 survivors. Patients mainly manifested bilateral knee and hip joint pain, flexion contracture of hip, limitation in internal and external rotation of hip; a few had arthritic functional disorder, deformation, and limp. The radiography illustrated shallow acetabulum with increased inclination, which encompassed the femoral head badly. Deformation of the femoral head, narrow joint space and osteophyte were also found by X-ray examination. The main risk factors of DDH were genetic factors, gender, birth season etc. The son or daughter with one or two DDH parents had a higher risk for developing DDH than those with no DDH parents. Furthermore, first-degree relatives of the DDH patients also had a greater chance to develop DDH than second-degree relatives and third-degree relatives. The incidence among females was higher than males, and the family member who was given birth in winter had a highest risk for developing DDH. However, there was no difference between incidence of DDH in children and youths and in adults; the incidence of DDH in the immigrants with no blood relationship also did not differ from the incidence of DDH in the family member.

CONCLUSIONThe genetic factors play an important role in the development of DDH, so do the environmental factors.

Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Child ; Family Health ; Female ; Hip Dislocation, Congenital ; diagnosis ; genetics ; Humans ; Male ; Middle Aged ; Pedigree ; Risk Factors ; Sex Factors ; Young Adult

OBJECTIVETo observe the occurrence of anastomotic bleeding following laparoscopic and open radical resection for rectal carcinoma, and to explore its contributing factors.

METHODSTwo hundred and sixty-three cases of rectal carcinoma undergone radical resection were divided into 2 groups, laparoscopic surgery (LS) group (n=86) and open surgery (OS) group (n=177). According to the different locations of anastomotic stoma and with or without preventive colostomy, the two groups were divided into AR sub-group and LAR/UAR sub-group, colostomy sub-group and non-colostomy sub-group. After analyzing the incidence of anastomotic bleeding in each sub-group, a logistic regression model was established to determine the relationships between anastomotic bleeding and three contributing factors including surgical approaches (LS or OS), location of stoma (AR or LAR/UAR) and preventive colostomy.

RESULTSAnastomotic bleeding occurred on 16 out of 263 patients with radical resection of rectal cancer (6.1%). The rates of anastomotic bleeding in LS group and OS group were 9.3% and 4.5%, in colostomy and non-colostomy were 8.1% and 5.5%, and in AR group and LAR/UAR group were 3.3% and 12.1% respectively, there were no significant differences between them (P>0.05). Comparing the two different surgical approaches (LS vs OS), the coefficient of regression, odd ratio and standard coefficient of regression for LS were 1.319, 3.741 and 0.342 respectively. In comparison of the locations of anastomosis (AR vs LAR/UAR), the three index for LAR/UAR were 2.460, 11.704, and 0.632 respectively. Comparing colostomy with non-colostomy, the three index for colostomy were -1.394, 0.248, and -0.327 respectively.

CONCLUSIONSAnastomotic bleeding after radical rectectomy is related to the choice of surgical approach, location of anastomosis and with or without preventive colostomy. Both LS and LAR/UAR are risk factors, and preventive colostomy is a protective factor. Regarding to the significance of three factors, location of anastomosis takes the first place, following by surgical method and with or without preventive colostomy.

Adult ; Aged ; Aged, 80 and over ; Anastomosis, Surgical ; adverse effects ; Colostomy ; adverse effects ; Female ; Humans ; Laparoscopy ; adverse effects ; Male ; Middle Aged ; Postoperative Hemorrhage ; etiology ; Rectal Neoplasms ; surgery