BackgroundSchizophrenia is a common severe mental disorder with complex pathogenesis. There are few studies on the correlation between kynurenine metabolites in peripheral serum and urine in schizophrenia. ObjectiveTo investigate the concentration of tryptophan-kynurenine metabolites and interleukin-6 （IL-6） in serum and urine in patients with schizophrenia， and their correlation with clinical symptoms， so as to explore potential biological characteristics related to schizophrenia. MethodsA total of 38 patients with schizophrenia who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， and were hospitalized or attended outpatient clinic at Hangzhou Seventh People's Hospital from December 2021 to December 2022 were included in the study. Additionally， 26 healthy individuals were concurrently recruited from the community of Hangzhou to serve as a control group. All participants were requested to complete the Positive and Negative Symptom Scale （PANSS）. The levels of tryptophan （TRP）， kynurenine （KYN）， kynurenic acid （KYNA）， quinolinic acid （QUIN）， picolinic acid （PIC）， xanthurenate and 5-hydroxytryptamine （5-HT） in both serum and urine were measured using ultra-high-performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry. Serum and urine IL-6 were measured using enzyme-linked immunosorbent assay. Pearson correlation analysis was conducted to examine the correlation between serum and urinary KYN metabolites， as well as the correlation between metabolite levels and clinical symptoms in the patient group. ResultsPatients with schizophrenia had significantly higher level of IL-6 in serum （U=798.500， P<0.01） and lower level of PIC in urine （U=253.000， P=0.013） compared with the control group. Additionally， level of serum KYN was positively correlated with QUIN/KYNA ratio and QUIN/PIC ratio （r=0.562， 0.438， P<0.05） in patients with schizophrenia. 5-HT/KYN ratio in serum was positively correlated with PANSS total score and negative symptom subscale score （r=0.458， 0.455， P<0.01） in patients with schizophrenia. ConclusionSerum TRP-KYN pathway metabolite levels in patients with schizophrenia were associated with neurotoxic metabolite ratios in urine and the severity of negative symptoms. ［Funded by Zhejiang Medical and Health Science and Technology Program Exploratory （number， 2022KY990）］

Objective To study the effect and mechanism of high glucose on mesothelial-mesenchymal transition(MMT)of peritoneal mesothelial cells(HMrSV5),and the protective effect of pharmacological blocking of signal transducer and activator of transcription 3(STAT3)on rat peritoneal fibrosis(PF)model.Methods The animals were divided into three groups:the sham group,the model group,and the STAT3 inhibitor group.A miniature per-itoneal dialysis catheter was implanted under the dorsal skin of rat and the rat peritoneal fibrosis model was induced by daily injection of high glucose dialysate.After 10 weeks,HE staining was used to evaluate the histology of the peritoneum,and the level of transforming growth factor-β1(TGF-β1)in the peritoneum was measured by immuno-histochemistry.HMrSV5 was cultured in high glucose and the optimal stimulation concentration of high glucose was determined by Western blot.High glucose was used to stimulate HMrSV5 after successful transfection with si-STAT3 and Western blot was used to measure the protein level of STAT3,p-STAT3,and the key enzymes of glycol-ysis 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)and lactate dehydrogenase A(LDHA).Results HE staining showed that administration of STAT3 inhibitor(BP-1-102)could inhibit the thickening of subperitoneal tissue and the proliferation of vessels in HG dialysis rats.The expression of TGF-β1 in the rats perito-neum of the model group was significantly higher than that in the sham group,and the level of TGF-β1 was marked-ly lower in the STAT3 inhibitor group compared to the model group(P<0.05).Compared to the control group,high glucose induced the up-regulation of α-smooth muscle actin(α-SMA),the down-regulation of E-cadherin and STAT3 activation in HMrSV5(P<0.05).Mesothelial cells treated with high glucose also exhibited high expres-sion of the key enzymes of glycolysis(PFKFB3,LDHA)(P<0.05),and si-STAT3 can effectively inhibit the overexpression of PFKFB3 and LDHA induced by high glucose(P<0.05).Conclusion STAT3 is involved in high glucose-induced HMrSV5 hyperglycolysis and MMT,and targeting STAT3 alleviates peritoneal fibrosis and an-giogenesis during peritoneal dialysis treatment in rats.

Objective To investigate the effects of hypothyroidism and drug intervention on the cognitive function of rat offspring through the establishment of a rat model of experimental hypothyroidism in pregnancy.Methods A to-tal of 20 SD female rats were randomly divided into control group(CON group)and hypothyroid group(PTU group).The hypothyroid model was established by propylthiouracil(PTU),the thyroid hormone levels of female mice were detected by electrochemiluminescence immunoassay,and the differences between the two groups were compared.After successful modeling,the male mice were mated in cages,and the hypothyroid group was randomly divided into no intervention group(group Ⅰ),first trimester intervention group(group Ⅱ)and second and third tri-mester intervention group(group Ⅲ).The Morris water maze(MWM)experiment was used to test the learning and memory ability of the rats.The morphological structure of hippocampal neurons,the expression of nucleoprotein(NeuN)and synapse-associated protein(SYN)in mature neurons were observed by hematoxylin-eosin staining(HE),Nissl staining and immunohistochemistry.Results ① Compared with the CON group,the female mice in the PTU group had a significant increase in TSH and a significant decrease in FT4(P＜0.05).② In the positio-ning navigation test,the evasion latency of the pups in each group was gradually shortened.On the 5th day,the in-cubation period of group Ⅰ was significantly longer than that of groups CON,Ⅱ,Ⅲ(P＜0.05).There was little change between groups Ⅱ and Ⅲ and CON groups(P＞0.05).③ The residence time of group Ⅱ was significantly different from that in group Ⅰ during the space exploration stage(P＜0.05).There was a significant difference be-tween the number of pups crossing the platform in group Ⅰ and groups CON,Ⅱ and Ⅲ(P＜0.05).④ There was no significant difference between HE staining and Nissl staining in hippocampal tissues of rats in each group.How-ever,compared with the CON group,the average absorbance of NeuN and SYN proteins in the hippocampus of mice in groups Ⅰ,Ⅱ and Ⅲ was significantly reduced(P＜0.05).Conclusion Hypothyroidism will have adverse effects on the cognitive function and hippocampal neuron development of pregnant rats,and the effects of interven-tion on the cognitive function of offspring at different stages of pregnancy are different,the earlier the intervention,the smaller the damage to cognitive function.

Objective To investigate the interventional effect and mechanism of a novel ampelopsis hydrogel on dampness-heat accumulation syndrome of gouty arthritis. Methods A total of 90 patients with gouty arthritis who met the diagnostic criteria of western medicine and were differentiated as damp-heat accumulation syndrome of traditional Chinese medicine(TCM) were randomly divided into treatment group, control group and blank group, with 30 patients in each group. The blank group was treated with etoricoxib only, the control group was treated with etoricoxib combined with ampelopsis hydrogel, and the treatment group was treated with etoricoxib combined with external application of ampelopsis hydrogel. The clinical efficacy, time to symptom improvement, safety, comfort, changes in syndrome scores of TCM, serum inflammatory factors[C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), erythrocyte sedimentation rate (ESR)], NF-κB signaling pathway-related proteins, Visual Analogue Scale (VAS) scores for pain, and joint mobility were compared among the three groups before and after treatment. Results The total effective rates in the treatment group and control group were 93.33% and 90.00%, respectively, which were higher than 70.00% in the blank group (P < 0.05). The time for improvement of pain, redness, tenderness, and limited joint mobility in the treatment group was shorter than that in the control group and blank group (P < 0.05). After 7 days of treatment, the TCM syndrome score in the treatment group was lower than that in the control group and blank group, and the levels of serum CRP, TNF-α, and ESR and the expressions of NF-κB signalingpathway-related proteins P50 and P65 in the treatment group and control group were lower than those in the blank group (P < 0.05). After 7 days of treatment, the VAS score in the treatment group was lower than that in the control group and blank group, and the comfort score in the treatment group was higher than that in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions among the three groups (P>0.05). Conclusion The effect of ampelopsis hydrogel in treating gouty arthritis is better than that of ampelopsis paste, and its mechanism may be related to the regulation of the NF-κB pathway and inhibition of inflammatory factor expression. The hydrogel is easy to use, hygienic, and comfortable, and is expected to become a safe, effective, and convenient external medicine for gouty arthritis.

Objective To analyze the relationship between cognitive and psychiatric symptoms and serum folate,homocysteine(Hcy)and vitamin B12 in patients with Alzheimer's disease(AD).Methods Fifty-eight patients with AD who were treated in Hangzhou Seventh People's Hospital from March 2019 to April 2022 were retrospectively selected.According to the score of neuropsychiatric inventory questionnaire(NPI-Q),they were divided into observation group A(NPI-Q<14 points,36 cases)and observation group B(NPI-Q≥14 points,22 cases).Fifty-eight elderly persons who underwent physical examination during the same period were included in control group.The general data,serum folate,Hcy,vitamin B12 levels,mini-mental state examination(MMSE)score,NPI-Q score,clinical dementia rating(CDR)score were compared among the three groups.Results There was statistical significance in age comparison among the three groups(P<0.05),that is control group0.05).There were significant differences in MMSE,NPI-Q,CDR scores and serum folate,Hcy and vitamin B12 levels among the three groups(P<0.05).After controlling for variables,MMSE score was positively correlated with folate and negatively correlated with Hcy;NPI-Q score was negatively correlated with folate and vitamin B12,and positively correlated with Hcy;CDR score was negatively correlated with folate and vitamin B12,and positively correlated with Hcy(P<0.05).Serum Hcy levels in AD patients with emotional symptoms or psychiatric symptoms or impaired frontal lobe function were significantly higher than those in asymptomatic AD patients(P<0.05).Conclusion Detection of serum folate,Hcy,vitamin B12 levels is beneficial to the diagnosis of AD patients.

Objective:To revise the 2017 classification of irreducible intertrochanteric fractures and summarize reduction techniques of 2021 classification.Methods:A retrospective analysis was conducted of the 17 patients with irreducible intertrochanteric fracture who had been treated at Department of Orthopaedic Surgery, The Ninth People's Hospital of Shanghai, Shanghai Jiaotong University School of Medicine from January 2015 to December 2019. They were 7 males and 10 females, with an age of (73.2 ± 16.1) years. On the basis of 2017 classification, the irreducible intertrochanteric fractures were classified into 2 types in the present 2021 classification. Type Ⅰ were interlocking fractures which were further classified into 3 subtypes: type ⅠA were sagittal interlocking ones (7 cases), type ⅠB greater trochanter interlocking ones (one case) and type ⅠC lesser trochanter interlocking ones (one case). Type Ⅱ were separating fractures which were further classified into 4 subtypes: type ⅡA were sagittal separating ones (4 cases), type ⅡB coronal separating ones (one case), type ⅡC rotational separating ones(one case) and type ⅡD complete separating ones (2 cases). All patients were treated by closed reduction and intramedullary nailing with different reduction strategies corresponding to their fracture types (application of ejector rods, clamps or prying techniques, etc.). A total of 132 patients with reducible femoral intertrochanteric fracture who had been admitted during the same period were selected as the control group. The fracture reduction time, intraoperative blood loss and Harris hip score at the last follow-up were compared between the 2 groups.Results:The 2 groups were comparable because there was no significant difference in their preoperative general data ( P>0.05). Type ⅠA accounted for the highest proportion of irreducible intertrochanteric fractures [41.3% (7/17)], followed by type ⅡA [23.6% (4/17)]. The fracture reduction time [(44.6 ± 6.7) min] in the irreducible group was significantly longer than that in the control group [(39.2 ± 9.6) min] ( P<0.05). There was no significant difference in intraoperative blood loss or Harris hip score at the last follow-up between the 2 groups ( P>0.05). Conclusions:Compared with the "2017 classification" , the "2021 classification" is more concise and easy to remember, and can directly prompt the corresponding proper fracture reduction techniques. The patients with irreducible intertrochanteric fracture using proper reduction techniques can obtain functional recovery similar to that in the patients with reducible intertrochanteric fracture after reduction and fixation.

Objective:To observe clinical outcomes of the repair of traumatic nerve defects in the proximal upper extremities by human acellular nerve allograft(hANG).Methods:Nerve defects in the upper extremities in 8 patients were repaired by hANG from March 2017 to January 2019. The patients were 6 males and 2 females with mean age of 35.4 (21-53) years old. The nerve defects were 2 radial nerve in distal upper arm, 4 median nerve in forearm, 1 interosseous dorsal nerve and 1 ulnar nerve in forearm. All injuries were acute nerve injury. Two patients had combined injury of upper arm muscle, 4 of forearm muscle and 1 of brachial artery defect. All wound were moderate to severe contaminated. The length of nerve defects was 30-60 (mean 45) mm. The surgical procedures were fixation of fracture, repair of the muscle and discovery of the broken ends of nerve and to repair with hANG. The postoperative follow-up period ranged 18 to 40 (mean 30.6) months to observe the local response of recovery. The efficacy was evaluated by the Upper Extremity Function Evaluation Standard set up by Hand Surgery Branch of Chinese Medical Association and Grading Standard of Muscle Strength.Results:No graft rejection was observed in all cases. Primarily healing was in 5 patients. Delayed healing in 2 patients and free skin grafting was performed. Local flap transfer was performed to repair the wound in 1 patient who developed a skin necrosis 10 days after surgery. Two patients with median nerve defects had nerve function restored well. The strength of finger grip and thumb opposition muscle restored to grade IV and the sensory function had restored S 3+. The interosseous dorsal nerve in 1 patient restored well. The strength of extensor digitorum tendon had restored to grade IV. Based on the evaluation criteria for the upper extremity issued by the Hand Surgery of the Chinese Medical Association, 3 patients was rated in excellent for function recovery, 1 in fair and 4 in poor. Conclusion:After throughout debridement, hANG can be applied in the repair of traumatic nerve defect in the proximal upper extremity in an emergency surgery and it can partially restore the nerve function.

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.

Objective:To increase the understanding of neuroleptic malignant syndrome, rhabdomyolysis and acute renal injury in advanced-aged patients with Parkinson's disease after abdominal surgery.Methods:We report a case of malignant syndrome, rhabdomyolysis and acute renal injury in an 85-year-old patient with Parkinson's disease after abdominal surgery in our department.The diagnosis and successful treatment experience were summarized, and a literature review was conducted.Results:The body temperature was as high as 40.5℃ in this patient, accompanied by stiffness, sustained involuntary shaking, increased muscle tone, serum creatine kinase at 104 615 U/L, tachycardia, low blood pressure, accelerated breathing rate, disturbance of consciousness, excessive sweating and other clinical manifestations, which met the diagnostic criteria for neuroleptic malignant syndrome.The patient had complications including concurrent rhabdomyolysis, acute renal injury and shock.The emergency was resolved after an early diagnosis and proactive treatment.Conclusions:If patients with Parkinson's disease have a high fever with rigidity or sudden aggravation within a short period of time after medication, the possibility of neuroleptic malignant syndrome should be considered and the causes should be screened.

The nail and nail bed are indispensibal structures with important function and esthetics role on the tip of fingers. Injury of the nail and nail bed often seriously affect the appearance and function of the fingers. The correct and timely treatment is essential for the restortation of good function according to the typing and degreement of the injuries. This paper reviewed about the function of nail and nail bed, typing of injury, evaluation of therapeutic effect and reconstruction of nail bed injury.