This paper aims to review treatment delay in first-episode schizophrenia,depression,and bipolar disorder,and to compare related factors of treatment delay in the three first-episode mental disorders.It is found that increased patient responsibility,stigma,lack of disease-related knowledge,lack of access to resources,and insuffi-cient medical support lead to delay treatment,and making patients to have longer course,heavier symptoms,and lower social functions.

Objective To explore the pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Methods The pharmacological model of hyperuricemia was established.The chemical components in vivo and in vitro of Simiao Wan were analyzed by UPLC-Q-Exactive-MS.Based on the components absorbed in blood,the"active ingredient-target-pathway"network of Simiao Wan for regulating hyperuricemia and gout was constructed by network pharmacology method.The key ingredients were used for molecular docking with key targets[uricogenase(XDH),uric acid transporter(ABCG2,GLUT9,OAT1,URAT1)and inflammatory targets(PTGS2,TLR2,TLR4)]of hyperuricemia and gout.Finally,experimental verification was conducted according to the results of molecular docking.Our aim is to identify the key pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Results Eighty-nine components of Simiao Wan were identified by UPLC-Q-Exactive-MS analysis,including 74 components absorbed in blood,which were confirmed as candidate ingredients.Network pharmacology was used to constructed"components absorbed in blood-target-pathway"network,and components absorbed in blood were matched with 116 targets of hyperuricemia and 173 targets of gout.It is involved in the regulation of biological processes,such as glucose and lipid metabolism,oxidative stress,inflammatory response,ERK1 and ERK2 cascade,MAPK cascade,PI3K signal transduction.Moreover,Simiao Wan plays a role in regulating the network of hyperuricemia and gout through regulating blood lipids and atherosclerosis,apoptosis,AGE-RAGE,TNF,PI3K-Akt,MAPK,TLRs,JAK-STAT,NF-κB and other signaling pathways.Molecular docking studies showed that berberine,phellodendrine,magnoflorine,jatrorrhizine,palmatine,obacunone,limonin,atractylodin,taxifolin,atractylenolide Ⅲ and β-ecdysterone had good affinity with uric acid synthase,uric acid transporter and inflammatory targets.Western Blot test showed that taxifolin negatively regulates the expression of URAT1.The above-mentioned compounds were the main pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Conclusion This article describes the main pharmacodynamic substances of Simiao Wan in the regulation of hyperuricemia and gout,which can provides a scientific basis for the clinical application,improvement in quality evaluation and standard of Simiao Wan.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Objective: To analyze the effect of body mass index (BMI) on the number of lymph nodes (LNs) harvested in patients who underwent colorectal cancer resection. Methods: A retrospective analysis of 328 patients with colorectal cancer who were treated at Fujian Provincial Hospital between December 2014 and January 2017 was conducted. All patients underwent colorectal cancer resec-tion and were assigned into 2 groups:<12-LN group and≥12-LN group. Potential clinicopathological variables that might influence the number of LNs harvested were statistically analyzed. Results: Univariate analyses demonstrated that BMI (χ2=7.697, P=0.006), tumor location (χ2=7.900, P=0.048), and TNM stage (χ2=34.795, P<0.01) affected the number of LNs harvested. Logistic regression analysis re-vealed that BMI of≥25 kg/m2 and rectosigmoid location were associated with 2.557-and 1.731-fold increases in the number of LNs harvested, compared with BMI<25 kg/m2 group and other tumor locations, respectively. Conclusions: Higher BMI may decrease the number of LNs harvested in patients who underwent colorectal cancer resection and could affect the postoperative pathological stage. K

OBJECTIVE: To investigate the safety of the controllable ileostomy with pipe in view of histology. METHODS: Twenty-eight Beagle dogs undergoing controllable ileostomy with pipe were studied. The special fistula tube with balloon was placed into the hole locating at the cecal root opposing the mesenteric side, and fixed by double knot compression method. RESULTS: The fistula tube was removed 14 days after surgery, then the safety of the procedure was preliminarily evaluated by gastrointestinal radiography and anatomical observation. The small intestine tissue at the compression suture was used as the experimental segment, and the small intestine tissue at the proximal non-compression suture was used as the control segment. The histological staining and the immunohistochemical staining of S-100 protein, c-kit protein and α-smooth muscle actin(α-SMA) protein between two segment were compared, while quantitative comparison of myenteric plexus, intestinal Cajal cell(ICC) and smooth muscle cells in intestinal wall was carried out. After removal of fistula tube at 14 days postoperative, the dogs were normal in feeding and defecation. The digestive tract radiography showed that the intestine was patent without obvious stenosis and obstruction. The dogs were dissected 21 days after operation. The abdominal sinus ostium was well healed and the internal sinus was well formed. Under gross inspection, blood supply, morphology and motor function of experimental intestine segment were similar from the proximal and distal segments of control intestine. S-100 immunohistochemical staining showed that the morphology and distribution of S-100 protein positive cells and "blank area" cells in the experimental and control segments were consistent. Myenteric plexus counting showed that the experimental segment was 3.62±1.82/field and the control segment was 3.27±1.62/field, whose difference was not statistically significant(t=1.30, P=0.20). Immunohistochemical staining of c-kit showed that the distribution of c-kit positive cells in both segments was consistent. Counting of the number of ICCs in myenteric plexus revealed that experimental segment was 2.96±2.57/plexus, and control segment was 2.49±1.80/plexus without significant difference(t=1.81, P=0.07). Immunohistochemical staining of α-SMA showed that the morphology and distribution of smooth muscle cells in whole intestinal wall(muscle layer, longitudinal muscle, ring muscle) in experimental and control segments were consistent. The average absorbance(A) value of α-SMA staining in ring muscle layer was detected and quantified. The experimental segment was 0.15±0.03 and control segment was 0.14±0.04 without significant difference(t=1.16, P=0.25). CONCLUSION The technique of controllable ileostomy with pipe is safe in view of histology, which may replace the traditional protective ileostomy.
Animals ; Dogs ; Ileostomy ; methods ; standards ; Intestine, Small ; surgery ; Models, Animal ; Proto-Oncogene Proteins c-kit ; metabolism ; Treatment Outcome

Objective To clarify the role of microsurgery in limb salvage procedure and its efficiency in long-term functional results through a retrospective review of patients who sustained severe injury of lower extremities and had been treated Shanghai 6th people's hospital, in recent 10 years. Methods Patients who sustained severe injury of lower extremities and treated with microsurgical techniques in January, 2006 to January, 2016 were studied. Patients' general information, classification of open fracture, and MESS were noted. The enrolled patients were divided into two groups (group A: primary microsurgical reconstruction;group B: non-microsurgical reconstruction ) according to whether primary microsurgical reconstruction was performed or not. Each group were also further divided into sub-group according to preoperative MESS (MESS<7 and MESS≥7). The reconstruction methods, hospitalization days, op-eration times, postoperative complications, as well as the SIP were then recorded for each groups. The differences of these data among each groups were analyzed and compared. Results The main objection was patient with Gustilo grade III open fracture, totally 548 patients were admitted, with 312 males and 236 females. The main age was 35.6 years old. The main etiology was road traffic accident (79.7％). There were 211 patients (38.5％) in group A, and 337 patients (61.5％) in group B. In group A, there were 37 patients in subgroup one (MESS<7), and 174 patients in sub-group two (MESS≥7). The rate of delayed amputation was 2.8％, while the complication rate was 11.8％. In group B, there were 181 patients in subgroup one(MESS<7), and 156 patients in subgroup two (MESS≥7). The rate of delayed amputation was 4.0％, while the complication rate was 13.3％. In long-term survey, the average VAS score of group B was higher than that of group A, but no significant difference was noted. The average VAS scores in 2 year postopera-tively in the subgroups (MESS≥7) were higher than those in the other subgroups (MESS<7). The results of SIP scores were similar with VAS scores in two groups. Conclusion The techniques of microsurgery has been promoting the successful rates and outcomes for limb salvage procedure over the recent decades. Meanwhile, the current evaluating system for se-vere limb injury needs to be updated to meet the demands of ever-developing limb salvage techniques.

OBJECTIVETo study the management for the perineal incision after laparoscopic-assisted abdominoperineal resection for rectal cancer.

METHODSClinical data of 87 patients undergoing laparoscopic Miles operation for lower rectal cancer from June 2009 to February 2014 were collected and studied. Presacral space drainage group: presacral space drainage tube was applied in 42 patients. Combined drainage group: presacral space drainage tube combined with subcutaneous vacuum pressure suction was applied in 45 cases. In combined drainage group, except the presacral drainage tube, another drainage tube was placed subcutaneously and connected to a negative pressure ball, which was fixed on the lateral anterior of perineal wound by the further incision and drainage. After subcutaneous tube was placed for 2 weeks, as drainage fluid was limpid and <15 ml/d for 3 days, meanwhile no obvious pelvic fluid was detected by ultrasound, and the wound healed quite well without redness and edema, then the subcutaneous tube with the negative pressure ball could be removed.

RESULTSThere were 51 males and 36 females with the mean age of 26-78(56.9±10.8) years old. The laparoscopic Miles operation was successfully completed in all the cases without death and complications. The drainage tube was placed for 4-13(8.0±2.5) days in presacral space drainage group, and for 4-14(6.7±2.4) days in combined drainage group. The subcutaneous tube was placed for 14-24(15.8±3.0) days. The primary healing rate of perineal wound in presacral space drainage group and combined drainage group was 66.7%(28/42) and 91.1%(41/45) respectively, while the perineal wound infection rate was 21.4%(9/42) and 4.4%(2/45) respectively, whose differences between two groups were both significant (χ=7.911, P=0.005 and χ=5.674, P=0.017).

CONCLUSIONPresacral space drainage tube combined with subcutaneous vacuum pressure suction in laparoscopic-assisted abdominoperineal resection for rectal cancer has better efficacy and lower infection rate for perineal incision, which is worth wide application.

Objective To study the process conditions for new gel Capto DEAE ion exchange chromatography to purify prothrombin complexes concentrates.Methods After removal of cryoprecipitate by centrifugation, healthy human plasma was mixed with DEAE-Sephadex A-50 gel.After that, the gel were washed and eluted to obtain eluate; then, the eluate, after being ultrafiltered, was loaded on a column packed with Capto DEAE-gel for chromatography to prepare PCC which was later determined for activities of coagulation factors Ⅱ,Ⅶ,Ⅸ,Ⅹ and anticoagulation protein C, with their yield calculated.Besides, the protein concentration of PCC was determined using the Bradford method, based on which the specific activity of the four coagulation factors and protein C were calculated. According to the results, purification effect of Capto DEAE-gel on the PCC was analyzed. Results Under different experimental conditions, the yield and purity of the coagulation factors FⅡ,FⅨ and FⅩ were high, and the equilibrum degree of the three factors was good;however, the yield and purity of coagulation factor FⅦwere very low.When the three variables ( sodium citrate, NaCl and pH) in balanced solution, washing solution and elution were 0.020-0.028 mol/L, 0.10-0.15 mol/L and 6.9-7.2;0.012-0.020 mol/L, 0.10-0.15 mol/L and 6.9-7.2;0.005-0.012 mol/L, 2.4 mol/L and 7.2-7.5 , respectively,the yield and purity of PCC prepared from Capto DEAE-gel were good. Under this condition, yield of factor Ⅸ was ( 74.40 ±10.89 )% and purity of factor Ⅸ was ( 3.31 ±0.31 ) IU/mL.Under different experimental conditions, yield and specific activity of anticoagulant protein C were higher.Conclusion The purity of four coagulation factors and anticoagulation protein C of PCC prepared by the new method that combined the batch adsorption with DEAE-sephadex A-50 was combined with column chromatography packed with Capto DEAE-gel are higher than those prepared by the routine procedure.Furthermore, the PCC are better than these products obtained by traditional process, whose purity are 2.17-3.31IU/mg.Therefore, these studies will lay the groundwork for exploring novel preparation process of producing PCC.