Advances in biotransformation of methanol into chemicals / 生物工程学报

Methanol has become an attractive substrate for the biomanufacturing industry due to its abundant supply and low cost. The biotransformation of methanol to value-added chemicals using microbial cell factories has the advantages of green process, mild conditions and diversified products. These advantages may expand the product chain based on methanol and alleviate the current problem of biomanufacturing, which is competing with people for food. Elucidating the pathways involving methanol oxidation, formaldehyde assimilation and dissimilation in different natural methylotrophs is essential for subsequent genetic engineering modification, and is more conducive to the construction of novel non-natural methylotrophs. This review discusses the current status of research on methanol metabolic pathways in methylotrophs, and presents recent advances and challenges in natural and synthetic methylotrophs and their applications in methanol bioconversion.

Recent advances in deorphanization of GPR35 and its functions in related diseases / 药学学报

G protein-coupled receptors (GPCRs) represent the largest family of membrane proteins and are the target of approximately half of all therapeutic drugs. There are ～300 orphan GPCRs, which have great potential in drug development. G protein-coupled receptor 35 (GPR35), a rhodopsin-like orphan GPCR, is widely involved in immune regulation, gastrointestinal disorders, cardiovascular diseases, cancer, as well as other diseases, suggesting its great potential as a therapeutic target in a variety of diseases. However, the current research on GPR35 is insufficient, including the true endogenous ligand has not been confirmed, the molecular mechanism of its role in disease is not fully understood, and there is a lack of effective intervention strategies targeting GPR35. This article summarizes the deorphatization of GPR35, GPR35-related signaling pathways and their association with various diseases, in order to provide a reference for in-depth study of GPR35 in diseases and development of drugs targeting GPR35.

Activation characteristics of motor cortex during mirror visual feedback based on electroencephalography / 中国康复理论与实践

ObjectiveTo explore the activation of motor cortex and brain lateralization of healthy male subjects during mirror visual feedback (MVF) of dominant and non-dominant hands. MethodsFrom March to September, 2021, 17 right-handed male subjects were recruited in Shenyang Sport University. The eegoTMmylab electroencephalography (EEG) system was applied to acquire the EEG and surface electromyography (sEMG) signals of digital extensor muscle during MVF. The subjects were completed unilateral finger stretching exercise, including left/right hand MVF and left/right hand visual feedback (VF). Each paradigm was repeated 80 trials, and the four paradigms were divided into two experiments, with one week between each experiment. The time-domain characteristics of sEMG signals and the time-frequency characteristics of α-band (8 to 13 Hz) and β-band (13 to 20 Hz) EEG signals which were closely related to motion were analyzed. Activation and asymmetry of motor cortex during MVF in dominant and nondominant hands were measured with event-related desynchronization/synchronization (ERD/ERS) and asymmetric index (AI). ResultsWhen the relaxed hand was right hand, the sEMG amplitude of digital extensor muscle were more in MVF and VF than in resting state (P < 0.05). In α bands, the main effect of training state on ERD/ERS was significant (F = 14.125, ηp2 = 0.469, P = 0.002), and it was higher in MVF than in VF. In β band, the main effect of training state on ERD/ERS was significant (F = 9.704, ηp2 = 0.378, P = 0.007), the interaction effect of moving hand and training state was significant on ERD/ERS (F = 8.014, ηp2 = 0.334, P = 0.012); for VF, ERD/ERS was higher in right hand movement than in left hand movement (F = 7.267, ηp2 = 0.312, P = 0.016); for right hand movement, ERD/ERS was higher in MVF than in VF (F = 17.530, ηp2 = 0.523, P = 0.001). At the position of C4 electrode, ERD/ERS was higher in right hand movement than in left hand movement under VF (t = -3.201, P = 0.006, Cohen's d = 0.776), and ERD/ERS was higher in MVF than in VF under right hand movement (t = -4.060, P = 0.001, Cohen's d = 0.985). Main effect of training state was significant on AI at β band (F = 5.796, ηp2 = 0.266, P = 0.028), and it was higher in MVF than in VF. ConclusionMVF may improve the activity of motor cortex neurons on the ipsilateral side of the motor hand through recruitment of frontal and parietal mirror neurons and reduction of interhemispheric and intracortical inhibitory activities, and it is more effective for the dominant hand training.

Monitoring and analysis of endemic situation of schistosomiasis in Suzhou New District from 2004 to 2021 / 上海预防医学

ObjectiveTo analyze the monitoring data of schistosomiasis from 2004 to 2021 in Suzhou New District， Jiangsu Province， and to provide evidence for improving schistosomiasis elimination strategies. MethodsFollowing the Opinions on Prevention and Control of Schistosomiasis， Parasitic Diseases and Endemic Diseases in Suzhou and the Technical Plan for Prevention and Control of Schistosomiasis， Parasitic Diseases and Endemic Diseases in Suzhou， the monitoring of schistosomiasis in the population and snail habitats from 2004 to 2021 was conducted. The Mann-Kendall method and Joinpoint regression method were employed to analyze the trend of epidemic indicators （such as seropositive rate， prevalence of snail frames， etc.）. Time series analysis （exponential smoothing model） was conducted to predict snail occurrence. ResultsFrom 2004 to 2021， a total of 73 680 people were serologically tested for schistosomiasis， with a positive rate of 0.084%. The seropositivity rate showed statistically significant differences between different years （χ2=70.73， P<0.05）， but there was no significant trend over time. In addition， 3 053 fecal tests were conducted and no positive result was found. The snail habitats covered an area of 70.11 hm2 and showed a decreasing trend （Z=-1.97， P<0.05）. A total of 30 093 frames were surveyed， of which 19.038% contained snails. The difference in the prevalence of snail frames between different years was statistically significant （χ2=7 203.09， P<0.05）， with a decreasing trend in the prevalence of snail frames （Z=-2.05， P<0.05）. A total of 26 296 live snails were seized and density of live snails was 0.874 snails per frame， showing a decreasing trend in the density of live snails （Z=-2.35， P<0.05）. A total of 12 391 snails were dissected and no infected snail was found. The areas treated with molluscicides remained stable at 264.60 hm2. An area of 27.77 hm2 achieved the goal of snail eradication through environmental modification， with a decreasing trend （Z=-2.44， P<0.05）. It is estimated that the prevalence of snail frames and snail density will remain relatively stable from 2022 to 2026， but the snail habitat area will fluctuate significantly， showing an increasing trend. ConclusionNo indigenous cases of schistosomiasis and no infected snails are reported， indicating the successful consolidation of schistosomiasis prevention and control measures. However， the snail habitat area fluctuates greatly with an increasing trend， suggesting the need for long-term Oncomelania snail monitoring in local areas.

Study on the correlation between triglyceride glucose index and severe hypertriglyceridemic pancreatitis / 中华消化杂志

Objective:To investigate the correlation between triglyceride glucose (TyG) index and severe hypertriglyceridemic pancreatitis (HTGP), and to provide assistance for early evaluation and clinical decision-making of HTGP.Methods:From January 2016 to December 2021, the clinical data of 770 patients diagnosed with HTGP at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were retrospectively collected. According to severity of pancreatitis, the patients were divided into mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) groups, and the differences in TyG index among the 3 groups was compared. According to the quartile range of the TyG index, the patients were divided into TyG Q1, Q2, Q3 and Q4 groups, and the distribution of severity of pancreatitis in each TyG index quartile group was calculated. Kruskal-Wallis H test was used for statistical analysis. Spearman correlation analysis was used to analyze the correlation between TyG index quartile range and the severity of pancreatitis. Linear trend chi-square test was used to analyze the trend of SAP incidence among groups. Binary logistic regression was used to analyze the relationship between TyG index quartile range and the risk of SAP, and the trend test was also conducted. Results:A total of 770 patients with HTGP were included, among them 330 (42.9%), 268 (34.8%) and 172 (22.3%) were MAP, MSAP and SAP, respectively. The TyG indices of MAP, MSAP and SAP group were 11.8(11.3, 12.4), 12.5(11.9, 13.2) and 12.7(12.1, 13.4), respectively, and the differences among the 3 groups were statistically significant ( H=121.77, P<0.001). The TyG index was 12.21 (11.57, 12.94) in the 770 patients. There were 192, 193, 193 and 192 patients enrolled in TyG Q1(TyG index <11.57)、 Q2(TyG index ranged from 11.57 to <12.21)、 Q3(TyG index ranged from 12.21 to <12.94) and Q4(TyG index≥12.94) group, respectively.The correlation test showed that the difference between TyG quartile range and the severity of pancreatitis was statistically significant ( ρ=0.372, P<0.001). The incidence of SAP in TyG Q1, Q2, Q3 and Q4 group was 10.9%(21/192), 14.5%(28/193), 27.5%(53/193) and 36.5%(70/192), respectively. The trend test of SAP incidence among the TyG gruops was statistically significant ( χ2 =44.33, P<0.001). After adjusting for confounding factors, taking the TyG Q1 group as a reference, the OR values of SAP risk (95% confidence interval) of the TyG Q2, Q3 and Q4 groups were 1.250 (0.619 to 2.524), 2.882 (1.506 to 5.514) and 6.660 (3.456 to 12.836), respectively, and the trend test of SAP risk showed a significant difference ( OR=2.508, 95%confidence interval 1.883 to 3.341, P<0.001). Conclusions:There is a correlation between TyG index and severity of pancreatitis in patients with HTGP. As the TyG index increases, the risk of SAP increases in HTGP patients. TyG index may be an early predictor of severe HTGP.

Triglyceride-controlling during acute phase of hypertriglyceridemia induced pancreatitis / 中华消化外科杂志

Triglyceride-controlling is an important treatment for hypertriglyceridemia induced pancreatitis in acute phase. At present, there is no unified recommendation of acute pan-creatitis guidelines for triglyceride-controlling at home and abroad, leading to confusion in clinical treatment. Combined with the relevant literatures and current researches, the authors summarize the principles, commonly used methods, status quo, and our recommendations for triglyceride-controlling of acute hypertriglyceridemia induced pancreatitis, aiming to provide theoretical guidance for the standardized treatment of hypertriglyceridemia induced pancreatitis in the acute phase.

Clinical value of lymph node dissection of No. 14cd during pancreaticoduodenectomy in patients with pancreatic head carcinoma / 中华外科杂志

Objectives: To evaluate the positive rate of left posterior lymph nodes of the superior mesenteric artery (14cd-LN) in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma,to analyze the impact of 14cd-LN dissection on lymph node staging and tumor TNM staging. Methods: The clinical and pathological data of 103 consecutive patients with pancreatic cancer who underwent pancreaticoduodenectomy at Pancreatic Center,the First Affiliated Hospital of Nanjing Medical University from January to December 2022 were analyzed,retrospectively. There were 69 males and 34 females,with an age(M (IQR))of 63.0 (14.0) years (range:48.0 to 86.0 years). The χ2 test and Fisher's exact probability method was used for comparison of the count data between the groups,respectively. The rank sum test was used for comparison of the measurement data between groups. Univariate and multivariate Logistic regression analyzes were used for the analysis of risk factors. Results: All 103 patients underwent pancreaticoduodenectomy successfully using the left-sided uncinate process and the artery first approach. Pathological examination showed pancreatic ductal adenocarcinoma in all cases. The location of the tumors was the pancreatic head in 40 cases,pancreatic head-uncinate in 45 cases,and pancreatic head-neck in 18 cases. Of the 103 patients,38 cases had moderately differentiated tumor and 65 cases had poorly differentiated tumor. The diameter of the lesions was 3.2 (0.8) cm (range:1.7 to 6.5 cm),the number of lymph nodes harvested was 25 (10) (range:11 to 53),and the number of positive lymph nodes was 1 (3) (range:0 to 40). The lymph node stage was stage N0 in 35 cases (34.0%),stage N1 in 43 cases (41.7%),and stage N2 in 25 cases (24.3%). TNM staging was stage ⅠA in 5 cases (4.9%),stage ⅠB in 19 cases (18.4%),stage ⅡA in 2 cases (1.9%),stage ⅡB in 38 cases (36.9%),stage Ⅲ in 38 cases (36.9%),and stage Ⅳ in 1 case (1.0%). In 103 patients with pancreatic head cancer,the overall positivity rate for 14cd-LN was 31.1% (32/103),and the positive rates for 14c-LN and 14d-LN were 21.4% (22/103) and 18.4% (19/103),respectively. 14cd-LN dissection increased the number of lymph nodes (P<0.01) and positive lymph nodes (P<0.01). As a result of the 14cd-LN dissection,the lymph node stage was changed in 6 patients,including 5 patients changed from N0 to N1 and 1 patient changed from N1 to N2. Similarly,the TNM stage was changed in 5 patients,including 2 patients changed from stage ⅠB to ⅡB,2 patients changed from stage ⅡA to ⅡB,and 1 patient changed from stage ⅡB to Ⅲ. Tumors located in the pancreatic head-uncinate (OR=3.43,95%CI:1.08 to 10.93,P=0.037) and the positivity of 7,8,9,12 LN (OR=5.45,95%CI:1.45 to 20.44,P=0.012) were independent risk factors for 14c-LN metastasis; while tumors with diameter >3 cm (OR=3.93,95%CI:1.08 to 14.33,P=0.038) and the positivity of 7,8,9,12 LN (OR=11.09,95%CI:2.69 to 45.80,P=0.001) were independent risk factors for 14d-LN metastasis. Conclusion: Due to its high positive rate in pancreatic head cancer,dissection of 14cd-LN during pancreaticoduodenectomy should be recommended,which can increase the number of lymph nodes harvested,provide a more accurate lymph node staging and TNM staging.

Clinical analysis of 4 acute ischemic stroke children treated with endovascular thrombectomy / 中华儿科杂志

Objective: To assess the feasibility of endovascular thrombectomy (EVT) for the treatment of acute ischemic stroke (AIS) in children. Methods: Clinical data and follow-up information of 4 AIS children who received EVT in the Department of Intervention & Hemangioma at the Children's Hospital of the Capital Institute of Pediatrics from December 2020 to June 2021 were collected retrospectively. The vascular recanalization after EVT was assessed by the modified thrombolysis in cerebral infarction (mTICI) score. Efficacy outcomes were assessed with initial and postprocedural Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score, and the modified Rankin scale (mRS) score at 3 and 6 months after treatment. Safety assessments included perioperative complications and intracranial hemorrhage post-treatment. Results: A total of 5 EVT treatment were performed on 4 children with AIS, of whom 3 were male. The age of onset was 4.6, 13.8, 7.8, 8.0, 8.9 years, respectively. The time from symptom onset to initiation of EVT was 19.0, 25.0, 22.0, 4.0, 16.5 hours, respectively and all patients achieved successful recanalization of the vessel after EVT (mTICI≥2b). The PedNIHSS score was 39, 14, 25, 39, 24 before treatment and decreased to 8, 1, 12, 39, 5 at discharge. All the procedures were performed with no perioperative complications. Only 1 patient with congenital heart disease had a recurrent AIS with malignant brain oedema and brain hernia. Although the occluded vessels were successfully recanalized,the symptoms were not improved and this patient died after treatment abandonment. The other 3 patients achieved good recovery at 6 months postoperatively. The mRS score of 3 patients was 3, 1, 2 at 3 months after EVT and decreased to 2, 1, 1 at 6 months. Conclusion: EVT treatment may be feasible and safe for pediatric AIS due to large vessel occlusion even when the treatment was initiated 6 hours post stroke, but children with heart disease may have a dismal prognosis.

Effect of acupuncture on functional delayed gastric emptying after gastric cancer surgery based on enhance recovery after surgery / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture for functional delayed gastric emptying after gastric cancer surgery on the basis of routine treatment.@*METHODS@#A total of 80 patients with functional delayed gastric emptying after gastric cancer surgery were randomly divided into an observation group (40 cases, 3 cases dropped off) and a control group (40 cases, 1 case dropped off). The control group was treated with routine treatment, e.g. continuous gastrointestinal decompression. On the basis of the treatment in the control group, the observation group was treated with acupuncture at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Gongsun (SP 4), Sanyinjiao (SP 6), 30 min each time, once a day, 5 days as a course, 1-3 courses were required. The first exhaust time, remove gastric tube time, liquid food intake time and hospital stay were compared in the two groups, and the clinical effect was evaluated.@*RESULTS@#The first exhaust time, remove gastric tube time, liquid food intake time and hospital stay in the observation group were shorter than the control group (P<0.001).@*CONCLUSION@#On the basis of routine treatment, acupuncture could accelerate the recovery of patients with functional delayed gastric emptying after gastric cancer surgery.

Clinical characteristics and comprehensive treatment of patients with cleidocranial dysplasia / 中华口腔医学杂志

Objective: To summarize the clinical characteristics of patients with cleidocranial dysplasia (CCD) and analyze their treatment methods. Methods: From January 2000 to December 2020, patients with CCD who completed comprehensive treatment in the Department of Orthodontics and the First Dental Clinic, School and Hospital of Stomatology, China Medical University were retrospectively analyzed. A total of 14 CCD patients [7 males and 7 females, aged (16.1±4.5) years] were collected. There were 153 impacted permanent teeth in this study. In addition to the teeth that needed to be extracted due to special conditions, 147 impacted teeth were pulled into the dentition using closed traction. Patients were divided into adolescent group (≥12 years and<18 years, 10 patients) and adult group (≥18 years, 4 patients). Failure rate of traction was compared between the two groups. Factors affecting the success rate of closed traction such as vertical position of teeth (high, middle and low) and horizontal position of the teeth (palatal, median and buccal) were analyzed. Results: The incidence of maxillary impacted teeth [69.3% (97/140)] was higher than that of mandibular impacted teeth [40% (56/140)]. The difference was statistically significant (χ2=24.22, P<0.001). The supernumerary teeth were mainly located in the premolar area 61.4% (21/44), and most of them were in the palatal region of the permanent teeth 95.5% (42/44). They were generally located at the same height or the occlusal side of the corresponding permanent teeth. The success rate of closed traction was 93.9% (138/147). The success rate in the adolescent group [98.2% (108/110)] was higher than that in the adult group [81.1% (30/37)], and the difference was significant (χ2=14.09, P<0.05). Failure after closed traction of 9 teeth was found totally, including 7 second premolars. The success rate of traction in impacted second premolars at different vertical (χ2=11.44, P<0.05) and horizontal (χ2=9.71, P<0.05) positions in alveolar bone was different significantlly. The success rates of the second premolars were high (15/16), middle (12/13), low (2/7), and lingual palatine (10/17), median (19/19), lip-buccal (0/0), respectively. Conclusions: The closed traction of impacted teeth in patients with CCD was effective, and the age was the main variable affecting the outcome. The success rate of traction in impacted second premolars located in low position vertically or in palatal position was low, which required close observation during treatment.

Association of 24-hour urinary sodium excretion and 25-hydroxy vitamin D level with albuminuria in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:Using 24-hour urinary sodium excretion (24h-UNa) as the surrogate measure of sodium intake, to evaluate the joint association of 24h-UNa and serum 25-hydroxy vitamin D (25-OHD) levels with the risk of albuminuria in patients with type 2 diabetes mellitus (T2DM).Methods:This retrospective study included 670 hospitalized T2DM cases in the Department of Endocrinology and Metabolic Diseases, the First Affiliated Hospital of Zhengzhou University from January 2018 to October 2021. Patients were divided into the albuminuria-positive group or negative-group according to the level of 24-hour urinary albumin excretion (24h-UAE); They were also divided into the high-sodium group or low-sodium group according to the level of 24h-UNa; Patients were divided into the low-VD group or high-VD group according to the level of 25-OHD. Combining 24h-UNa and 25-OHD, the patients were further divided into four groups: high-VD low-sodium group ( n=85), high-VD high-sodium group ( n=122), low-VD low-sodium group ( n=248), and low-VD high-sodium group ( n=215). The effect of 24h-UNa and 25-OHD association on albuminuria was analyzed by binary regression. Results:There were significant differences in 24h-UAE level among the four groups ( P<0.01), the level of 24h-UAE in the low-VD high-sodium group was significantly higher than that in low-VD low-sodium group, high-VD low-sodium group, and high-VD high-sodium group [39.00(13.00, 319.00)mg/24 h vs 22.00(10.00, 99.00)mg/24 h, 22.00(9.00, 72.50)mg/24 h, 22.45(9.69, 72.75)mg/24 h; P=0.047, P=0.019, P=0.030]. Correlation analysis showed a positive correlation between 24h-UNa and 24h-UAE in the low-VD group ( P=0.017), but not in the high-VD group ( P=0.411). Binary regression analyses showed that both 24h-UNa ( P=0.017) and 25-OHD( P=0.023) were independent risk factors for positive albuminuria in patients with T2DM. The risk of positive albuminuria in the low-VD high-sodium group was 1.789 times higher than that in the high-VD low-sodium group ( P=0.037). Conclusion:24h-UAE in T2DM patients was affected by the combination of 24h-UNa and 25-OHD. A low level of 25-OHD increased the risk of albuminuria in high sodium intake T2DM patients.

Random sperm DNA fragmentation index is not associated with clinical outcomes in day-3 frozen embryo transfer / 亚洲男科学杂志(英文版)

Damage to sperm DNA was proposed to play an important role in embryonic development. Previous studies focused on outcomes after fresh embryo transfer, whereas this study investigated the influence of sperm DNA fragmentation index (DFI) on laboratory and clinical outcomes after frozen embryo transfer (FET). This retrospective study examined 381 couples using cleavage-stage FET. Sperm used for intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) underwent density gradient centrifugation and swim up processing. Sperm DFI had a negative correlation with sperm motility (r = -0.640, P < 0.01), sperm concentration (r = -0.289, P < 0.01), and fertilization rate of IVF cycles (r = -0.247, P < 0.01). Sperm DFI examined before and after density gradient centrifugation/swim up processing was markedly decreased after processing (17.1% vs 2.4%, P < 0.01; 65 randomly picked couples). Sperm progressive motility was significantly reduced in high DFI group compared with low DFI group for both IVF and ICSI (IVF: 46.9% ± 12.4% vs 38.5% ± 12.6%, respectively; ICSI: 37.6% ± 14.1% vs 22.3% ± 17.8%, respectively; both P < 0.01). The fertilization rate was significantly lower in high ( ≥25%) DFI group compared with low (<25%) DFI group using IVF (73.3% ± 23.9% vs 53.2% ± 33.6%, respectively; P < 0.01) but was equivalent in high and low DFI groups using ICSI. Embryonic development and clinical outcomes after FET were equivalent for low and high DFI groups using ICSI or IVF. In this study, sperm DFI did not provide sufficient information regarding embryo development or clinical outcomes for infertile couples using FET.

Technical recommendation for pragmatic randomized controlled trial of heat-sensitive moxibustion in community (Ⅰ): randomization with consideration of patient preference / 中国针灸

Heat-sensitive moxibustion is the appropriate technique of the external treatment in traditional Chinese medicine and it is widely used in community because of its "easy learning, simple operation and clear curative effect". Pragmatic randomized controlled trial is a main intervention design in the real world study, which provides a high-level evidence for the effectiveness assessment of heat-sensitive moxibustion in community management. Focusing on the key links of randomization, e.g. block randomization, stratified randomization, cluster randomization, sample size allocation, allocation concealment and blinding, the paper elaborates the advantages, disadvantages and technical details of two-stage randomization with consideration of patient preference in pragmatic randomized controlled trials of heat-sensitive moxibustion in community. It facilitates improving the quality of evidence, reproducibility and methodological homogeneity among different trials.

Establishment of a rat silicosis model via non-exposed tracheal instillation in combination with a ventilator / 中国职业医学

@#Objective - To establish a new non exposed intratracheal instillation method for establishing a rat silicosis model. Methods ， The specific pathogen free SD rats were randomly divided into control group and experimental group with ten rats in ， each group. Rats in the control group were given 1.0 mL of 0.9% sodium chloride solution and rats in the experimental group - were given 1.0 mL of silica suspension with a mass concentration of 50 g/L adopting to the one time intratracheal instillation ， - ， method and then followed by ventilator assisted ventilation immediately. When the tidal volume stabilized at 2.0 mL the ventilator was removed and the tracheal intubation was pulled out. Five rats in each group were sacrificed after two and four ， - Results weeks after modeling and hematoxylin eosin staining and Masson staining of lung tissue were performed. There was ， ， no death in the two groups of rats during the experiment. After two and four weeks the control group had normal lung structure ， ， ， normal alveolar cavity size no inflammatory cell infiltration thin alveolar wall only a small amount of collagen distribution ， around the lung interstitium and bronchus. At the second week of modeling the alveolar wall of the rats in the experimental ， ， ， group was slightly thickened interstitial lymphocytes and macrophages were infiltrated slight hyperplasia was found and a ， small amount of fibroblasts were visible. At the 4th week of modeling the alveolar wall of the rats in the experimental group was ， ， ， ， significantly thickened fibrous nodules were formed and fibroblasts fibrocytes collagen fibers were significantly increased. Conclusion - The combination of ventilator and non exposed intratracheal instillation method can be used to successfully ， ， . establish a rat silicosis model which is simple safe and effective

Comparative clinical efficacy analysis of pancreatoduodenectomy for distal bile duct and pancreatic head cancer: a report of 1 005 cases / 中华外科杂志

Objective: To compare and analyze the clinical efficacy of pancreaticoduodenectomy for distal bile duct cancer and pancreatic head cancer. Methods: Clinical data of 1 005 patients who underwent pancreaticoduodenectomy and postoperative pathological examination confirmed the diagnosis of distal bile duct cancer and pancreatic head cancer at the Pancreas Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were analyzed retrospectively. There were 112 cases in the distal bile duct cancer group, 71 males and 41 females,with age (M(IQR)) of 65(15) years(range: 40 to 87 years); 893 cases in the pancreatic head cancer group, 534 males and 359 females,with age of 64(13)years(range: 16 to 91 years). The differences between clinicopathological characteristics and postoperative overall survival of the two groups were analyzed by χ2 test, Fisher's exact probability method, rank sum test or log-rank test, respectively. The difference in postoperative overall survival between the two groups was compared using Kaplan-Meier method after propensity score matching (1∶1). Results: Compared with the pancreatic head cancer group,the distal bile duct cancer group had shorter operative time (240.0(134.0) minutes vs. 261.0(97.0) minutes, Z=2.712, P=0.007),less proportion of combined venous resection (4.5% (5/112) vs. 19.4% (173/893), χ²=15.177,P<0.01),smaller tumor diameter (2.0(1.0) cm vs. 3.0(1.5) cm,Z=10.567,P<0.01),higher well/moderate differentiation ratio (51.4% (56/112) vs. 38.0% (337/893), χ²=7.328, P=0.007),fewer positive lymph nodes (0(1) vs. 1(3), Z=5.824, P<0.01),and higher R0 resection rate (77.7% (87/112) vs. 38.3%(342/893), χ²=64.399, P<0.01),but with a higher incidence of overall postoperative complications (50.0% (56/112) vs. 36.3% (324/892), χ²=7.913,P=0.005),postoperative pancreatic fistula (28.6% (32/112) vs. 13.9% (124/893), χ²=16.318,P<0.01),and postoperative abdominal infection (21.4% (24/112) vs. 8.6% (77/892), χ²=18.001,P<0.01). After propensity score matching, there was no statistical difference in postoperative overall survival time between patients in the distal bile duct cancer group and the pancreatic head cancer group (50.6 months vs. 35.1 months,Z=1.640,P=0.201),and multifactorial analysis showed that tumor site was not an independent risk factor affecting the prognosis of patients in both groups after matching (HR=0.73,95%CI:0.43 to 1.23,P=0.238). Conclusions: Patients with distal bile duct cancer are more likely to benefit from early diagnosis and surgical treatment than patients with pancreatic head cancer,but with a relative higher postoperative complication rates. The different tumor origin site is not an independent risk factor for prognosis of patients with distal bile duct cancer and pancreatic head cancer after propensity score matching.

Approach to the patient with pituitary metastases initially manifested as central diabetes insipidus / 中华内分泌代谢杂志

The data of 10 patients with pituitary metastases were retrospectively analyzed, including tumor origin, clinical features, imaging characteristics, diagnosis and differential diagnosis, treatment and prognosis. The results showed that the average age of 10 patients at the time of consultation was 62.0 years. Nine metastases were originated from lung cancer and one from breast cancer. All patients started with central diabetes insipidus, and some of them accompanied with hypopituitarism, as well as occupancy manifestations such as headache, blurred vision, etc. MRI showed abnormalities in the pituitary stalk and posterior pituitary, four of which showed characteristic " dumbbell-shaped" changes. Three patients with epidermal growth factor receptor(EGFR)-mutated lung adenocarcinoma revealed improvement in both primary lesion and pituitary metastases after targeted therapy.

Vitamin D supplementation improves testicular function in aging rats induced by D-galactose / 中华内分泌代谢杂志

Objective:To investigate the effects and potential mechanism of vitamin D supplementation on testicular function in aging rats induced by D-galactose.Methods:The aging rats were induced by D-galactose with subcutaneous injection. The animals were randomly divided into 6 groups: aging rats (DG), aging rats with low-dose vitamin D supplementation (LD), aging rats with high-dose vitamin D supplementation (HD), normal control rats(NC), normal rats with low-dose vitamin D supplementation(LN), normal rats with high-dose vitamin D supplementation (HN). The body weight, testicular weight, serum testosterone concentrations and sperm quality of the rats in each group were measured. The testis morphological changes were detected using light microscopy. The activity of superoxide dismutase (SOD) and level of malondialdehyde(MDA) were determined with spectrophotometer. The expression levels of Nrf2, GCLC, SOD2 and VDR in testis were detected by western blot.Results:At baseline, compared with NC group, testicular weight, serum testosterone level, SOD activity, Nrf2, GCLC and SOD2 expression levels were significantly decreased in DG group, while MDA level was significantly increased. After vitamin D supplementation, testicular weight, testosterone levels and SOD activity in both of HD and LD groups were significantly increased, while the MDA level was significantly decreased. The expression levels of Nrf2, GCLC, SOD2 and VDR were significantly increased.Conclusion:Vitamin D supplementation may enhance the testicular antioxidant capacity through activating Nrf2-ARE signaling pathway, and improve the testicular function in D-galactose-induced aging rats.

Clinical efficacy of pancreaticoduodenectomy for periampullary diseases: a report of 2 019 cases / 中华消化外科杂志

Objective:To investigate the clinical efficacy of pancreaticoduodenectomy (PD) for periampullary diseases.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 2 019 patients with periampullary diseases who underwent PD in the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were collected. There were 1 193 males and 826 females, aged 63(15) years. Observation indicators: (1) surgical situations; (2) postoperative conditions; (3) postoperative pathological examinations; (4) prognosis of patients with periampullary carcinoma. Regular follow-up was conducted by telephone interview and outpatient examination once every 3 months within the postoperative first year and once every 6 months thereafter to detect the survival of patients with periampullary carcinoma. The follow-up was up to December 2021. Measurement data with skewed distribution were represented as M(IQR) or M(range), and comparison between groups was analyzed using the rank sum test. Count data were described as absolute numbers and (or) percentages, and comparison between groups was analyzed by the chi-square test or Fisher exact probability. Kaplan-Meier method was used to draw survival curves and calculate survival rates, and Log-Rank test was used to conduct survival analysis. Results:(1) Surgical situations: of 2 019 patients, 1 116 cases were admitted from 2016-2018 and 903 cases were admitted from 2019-2020. There were 1 866 cases undergoing open PD and 153 cases undergoing laparoscopic or robot-assisted PD. There were 1 049 cases under-going standard PD and 970 cases undergoing pylorus-preserved PD. There were 215 cases combined with portal mesenteric vein resection, 3 cases combined with arterial resection. The operation time of 2 019 patients was 255(104)minutes and the volume of intraoperative blood loss was 250(200)mL. The intraoperative blood transfusion rate was 31.401%(623/1 984), with the blood transfusion data of 35 cases missing. The proportions of pylorus-preservation, combination with portal mesenteric vein resection, intraoperative blood transfusion were 585 cases(52.419%), 97cases(8.692%), 384 cases(34.941%) for patients admitted in 2016-2018, versus 385 cases(42.636%), 118 cases(13.068%), 239 cases(27.006%) for patients admitted in 2019-2020, showing significant differences between them ( χ2=19.14,10.05,14.33, P<0.05). (2) Postoperative conditions: the duration of postoperative hospital stay of 2 019 patients was 13 (10) days. One of 2 019 patients lacked the data of postopera-tive complications. The overall postoperative complication rate was 45.292%(914/2 018), of which the incidence rate of grade B or C pancreatic fistula was 23.439%(473/2 018), the rate of grade B or C hemorrhage was 8.127%(164/2 018), the rate of grade B or C delayed gastric emptying was 15.312%(309/2 018), the rate of biliary fistula was 2.428%(49/2 018) and the rate of abdominal infection was 12.884%(260/2 018). The reoperation rate of 2 019 patients was 1.932%(39/2 019), the in-hospital mortality was 0.644%(13/2 019), the postoperative 30-day mortality was 1.238%(25/2 019), and the postoperative 90-day mortality was 2.675%(54/2 019). There were 541 cases(48.477%) with overall postoperative complications, 109 cases(9.767%) with grade B or C hemorr-hage, 208 cases(18.638%) with grade B or C delayed gastric emptying , 172 cases(15.412%) with abdominal infection, 39 cases(3.495%) with postoperative 90-day mortality of 1 116 patients admitted in 2016-2018. The above indicators were 373 cases(41.353%), 55 cases(6.098%), 101 cases(11.197%), 88 cases(9.756%), 15 cases(1.661%) of 902 patients admitted in 2019-2020, respectively. There were significant differences in the above indicators between them( χ2=10.22, 9.00, 21.30, 14.22, 6.45 , P<0.05). The in-hospital mortality occurred to 11 patients(0.986%) of 1 116 patients admitted in 2016-2018 and to 2 cases(0.221%) of 903 patients admitted in 2019-2020, showing a significant difference between them ( P<0.05). (3) Postoperative pathological examinations. Disease area of 2 019 patients reported in postoperative pathological examinations: there were 1 346 cases(66.667%) with lesions in pancreas, including 1 023 cases of carcinoma (76.003%) and 323 cases(23.997%) of benign diseases or low potential malignancy. There were 250 cases(12.382%) with lesions in duodenal papilla, including 225 cases of carcinoma (90.000%) and 25 cases(10.000%) of benign diseases or low potential malignancy. There were 174 cases(8.618%) with lesions in bile duct, including 156 cases of carcinoma (89.655%) and 18 cases(10.345%) of benign diseases or low potential malignancy. There were 140 cases(6.934%) with lesions in ampulla, including 134 cases of carcinoma (95.714%) and 6 cases(4.286%) of benign diseases or low potential malignancy. There were 91 cases(4.507%) with lesions in duodenum, including 52 cases of carcinoma (57.143%) and 39 cases(42.857%) of benign diseases or low potential malignancy. There were 18 cases(0.892%) with carcinoma in other sites. Postoperative pathological examination showed carcinoma in 1 608 cases(79.643%), benign diseases or low potential malignancy in 411 cases(20.357%). The histological types of 1 608 patients with carcinoma included adenocarcinoma in 1 447 cases (89.988%), intra-ductal papillary mucinous carcinoma in 37 cases(2.301%), adenosquamous carcinoma in 35 cases(2.177%), adenocarcinoma with other cancerous components in 29 cases(1.803%), neuroendocrine carcinoma in 18 cases(1.119%), squamous carcinoma in 1 case (0.062%), and other histological malignancies in 41 cases(2.550%). The histological types of 411 patients with benign or low poten-tial malignancy included intraductal papillary mucinous neoplasm in 107 cases (26.034%), chronic or autoimmune inflammatory disease in 62 cases(15.085%), neuroendocrine tumor in 58 cases(14.112%), pancreatic serous cystadenoma in 52 cases(12.652%), pancreatic solid pseudopapillary tumor in 36 cases(8.759%), gastrointestinal stromal tumor in 29 cases(7.056%), villous ductal adenoma in 20 cases(4.866%), pancreatic mucinous cystadenoma in 2 cases(0.487%), pancreatic or duodenal trauma in 2 cases(0.487%) and other histological types in 43 cases(10.462%). (4) Prognosis of patients with periampullary carcinoma. Results of survival analysis of 1 590 patients with main locations of periampullary carcinoma showed that of 1 023 patients with pancreatic cancer, 969 cases were followed up for 3.0-69.6 months, with a median follow-up time of 30.9 months. The median overall survival time, 1-year, 3-year and 5-year survival rates of pancreatic cancer patients were 19.5 months [95% confidence interval ( CI) as 18.0-21.2 months], 74.28%, 29.22% and 17.92%. Of 225 patients with duodenal papillary cancer, 185 cases were followed up for 3.0-68.9 months, with a median follow-up time of 36.7 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were unreached, 94.92%, 78.87% and 66.94%. Of 156 patients with distal bile duct cancer, 110 cases were followed up for 3.0-69.5 months, with a median follow-up time of 25.9 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were 50.6 months (95% CI as 31.4 to not reached), 90.37%, 56.11% and 48.84%. Of 134 patients with ampullary cancer, 100 cases were followed up for 3.0-67.8 months, with a median follow-up time of 28.1 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were 62.4 months (95% CI as 37.8 months to not reached), 90.57%, 64.98% and 62.22%. Of 52 patients with duodenal cancer, 38 cases were followed up for 3.0-69.5 months, with a median follow-up time of 26.2 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were 52.0 months (95% CI as 30.6 months to not reached), 93.75%, 62.24% and 40.01%.There was a significant difference in overall survival after PD between patients with different locations of periampullary malignancies ( χ2=163.76, P<0.05). Conclusions:PD is safe and feasible in a high-volume pancreas center, but the incidence of overall postoperative complications remains high. With the increase of PD volume, the incidence of overall postoperative complications has significantly decreased. There is a significant difference in overall survival time after PD among patients with different locations of periampullary malignancies. The 5-year survival rate after PD for duodenal papillary cancer, ampullary cancer, duodenal cancer and distal bile duct cancer is relatively high, whereas for pancreatic cancer is low.

Progress of discovery of molecular glues from natural products and their derivatives / 药学学报

Molecular glues are a class of small molecules that induce the formation of protein-protein interactions to confer new biological function or therapeutic effects. As a unique pharmacological modality, molecular glues could target proteins without druggable binding pockets. It exhibits a variety of functions, including regulating signal transduction, stabilization or degradation of targeted proteins, through sticking different proteins together. This review will summarize the development and current status of molecular glues derived from natural products and analogs by illustrating the discovery and interaction mechanism. We hope to present a systematic view, provide valuable clues for researchers and encourage them to explore more efficient and rational molecular glue discovery strategies.

Protective effects of Wuwei Xiaodu Drink against chronic osteomyelitis through Foxp3+CD25+CD4+ Treg cells via the IL-2/STAT5 signaling pathway / 中国天然药物

To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink (WWXDD) in inhibiting chronic osteomyelitis via regulatory T cells signaling. The effective constitutes of WWXDD and osteomyelitis related genes were screened. Target proteins were cross-validated using the Venny database. GO function and KEGG pathway analysis were performed for target proteins, while pharmacological network was constructed. The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA. The expression of CTLA-4 and Foxp3 mRNA and STAT5, p-STAT5, CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot, respectively. FACS was used to analyze the percentages of cells. A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes. Inflammation-related genes, including IL-6, TNFα, IL-1β and IL-2 showed high connection degree in the drug-compound-disease-target network. GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways, immune related pathways and chemokine signaling pathway. Furthermore, the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD. Meanwhile, the concentrations of IL-2 and CD4+CD25+Foxp3 Treg percentages together with the levels of p-STAT5, CTLA-4 and Foxp3 were also down-regulated. Furthermore, IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2, IL-10, TGF-β1, Foxp3, CTLA4 and STAT5. In addition, a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4. WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression. Our results bring a new solution for chronic osteomyelitis.