Objective To observe the effects of cyclic tensile strain (CTS) on in vitro expression of glycosaminoglycans (GAG) in rabbit chondrocytes of different ages.Methods Nine male New Zealand rabbits were grouped into juvenile (2 months), adult (8 months), and senior (31 months) groups. The bilateral knee joints were harvested using sterile technique from each rabbits. In each age group, rabbit articular chondrocytes were cultivated in vitro after randomization into a control group and a CTS group, with 6 specimens in each. In the next 3 days, CTS was applied (sin10％, 0. 5 Hz, 6 h/d) in the CTS group for 6 hours per day while no CTS was applied in the control group. After the first CTS treatment, the supernatant of cell culture was collected every 12 hours from each specimen in both groups to assess the GAG levels by Alcian blue assay.Results Expressions of GAG showed significant increases in both control and CTS groups in each age group ( P ＜ 0. 05) . Different age groups showed significant differences in the GAG secretion over different time points. Compared with the younger cells, the older ones showed the most significant difference in growth between the control and CTS groups at 12 hours, though the older cells produced less GAG than the younger ones in both groups at the end of the experiment (72 hours).Conclusions CTS can stimulate rabbit chondrocytes of different ages to secrete more GAG, and younger cells tend to produce more GAG than the older ones.

Background: Maedi/Visna virus (MVV) is a contagious viral pathogen that causes considerable economic losses to the sheep industry worldwide. Objectives: In China, MVV has been detected in several regions, but its molecular characteristics and genetic variations were not thoroughly investigated. Methods: Therefore, in this study, we conducted next-generation sequencing on an MVV strain obtained from northwest China to reveal its genetic evolution via phylogenetic analysis. Results: A MVV strain obtained from Inner Mongolia (NM) of China was identified. Sequence analysis indicated that its whole-genome length is 9193 bp. Homology comparison of nucleotides between the NM strain and reference strains showed that the sequence homology of gag and env were 77.1%–86.8% and 67.7%–75.5%, respectively. Phylogenetic analysis revealed that the NM strain was closely related to the reference strains isolated from America, which belong to the A2 type. Notably, there were 5 amino acid insertions in variable region 4 and a highly variable motif at the C-terminal of the surface glycoprotein (SU5). Conclusions The present study is the first to show the whole-genome sequence of an MVV obtained from China. The detailed analyses provide essential information for understanding the genetic characteristics of MVV, and the results enrich the MVV library.

Objective:To summarize the clinical phenotype and genetic characteristics of Poirier-Bienvenu neurodevelopmental syndrome associated with CSNK2B gene variation. Methods:The clinical and genetic data of a child with Poirier-Bienvenu neurodevelopmental syndrome caused by shear variant of CSNK2B gene who was diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in March 2022 were collected. Previous relevant literature at home and abroad was reviewed to summarize the clinical characteristics of the disease. Results:The child was a girl aged 13 months, mainly due to "intermittent convulsions for 2 months" for consultation. The clinical manifestations of the girl were normal face, generalized tonic-clonic seizures, low intelligence, language and motor retardation, and there was no abnormality in the long-range video electroencephalography and the head magnetic resonance imaging. No abnormality was found in chromosome karyotype analysis and chromosome coefficient of copy variation analysis. The whole exon gene sequencing test indicated that the child carried de novo heterozygous shear variant of CSNK2B gene c.291+5G>C, which had not been reported in the literature. According to the clinical manifestations and genetic examination results of the child, the diagnosis of Poirier-Bienvenu neurodevelopmental syndrome was clear. The CSNK2B gene of the proband′s parents and the twin sister was wild-type. The application of sodium valproate anti-seizure medication could effectively control the seizures of the child, and by giving rehabilitation function training, the child′s language and gross motor function was improved. Conclusions:The Poirier-Bienvenu neurodevelopmental syndrome is a rare autosomal dominant disorder caused by variants in the CSNK2B gene. The clinical manifestations are infancy-onset seizures, intellectual development disorders, language and motor development disorders, etc, and the video electroencephalogram and skull magnetic resonance are mostly normal. The CSNK2B gene shear variant is the genetic etiology of the proband.

Objective:To summarize the clinical phenotype and genetic characteristics of biallelic variation in HPDL leading to neurodevelopmental disorders with progressive spasticity and cerebral white matter abnormalities. Methods:The clinical and genetic data of 3 cases with neurodevelopmental disorders confirmed in the Department of Neurology of the Affiliated Children′s Hospital of Zhengzhou University from February 2018 to June 2022 were analyzed. The second-generation sequencing method was used to sequence the HPDL gene and the first-generation Sanger sequencing was used to verify the family members, and the characteristics of gene variants were summarized, and the 3 cases were treateds and followed-up. Results:Among the 3 children with neurodevelopmental disorders, 2 were females and 1 was male, and the age of onset was 25 days to 11 years of birth. In the clinical phenotypes, cases 1 and 2 were children with Leigh-like syndrome with infancy onset, with recurrent seizures, intelligent backwardness, language and motor delay, lactic acid increase, acidosis. Cranial magnetic resonance plain scan suggested deepening of the sulcus in the bilateral cerebral hemisphere, abnormal symmetrical signals in the basal ganglia, dorsal thalamus, cerebral peduncles and brainstem, expansion of the supratentorial ventricle, and thinning of the corpus callosum. And cranial magnetic resonance spectroscopy suggested visible lactate peaks in the measurement area of bilateral putamen lesions. Case 3 presented with spastic paraplegia, early motor retardation, and late spastic gait. The plain skull magnetic resonance imaging scan showed no abnormalities. In the 3 cases, the whole exon genome sequencing showed the heterozygous variant c.26_.28delGCC(p.Cys9_His10delinsTyr) and the parent missense heterozygous variant c.788C>T(p.Thr263Met), the paternal truncated variant c.1051C>T(p.Gln351 *) and the parent frameshift variant c.995de1C(p.Thr332Mfs * 9), the parent missense variant c.781C>G (p.Leu261Val) and the parent truncated variant c.721C>T (p.Gln241 *). The c.26_28delGCC(p.Cys9_His10delinsTyr) was an unreported site mutation. No abnormalities were found in chromosomal copy number variation and mitochondria-related genes. Cases 1 and 2 were treated with anti-seizure drugs and cocktail, and the seizure was under effective control; case 3 was treated with comprehensive treatment and rehabilitation function training, and exercise and intelligence were improved. Conclusions:The clinical phenotype of the biallelic variant in HPDL was Leigh-like syndrome and hereditary spastic paraplegia, characterized by compound heterozygous variant, including whole code, missense, frameshift, and truncated variants. Biallelic variation in HPDL was found to be the genetic etiology of the 3 probands.

Objective: To analyze the concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations detected in plasma and matched tumor tissues in colorectal cancer patients, in order to provide good evidences to support plasma could be a potential surrogate of tumor tissue for gene mutation test. Methods: One hundred and seventy-five cases of colorectal cancer were collected at the First Hospital of Jilin University, from October 2016 to October 2017.There were 101 males and 74 females, their ages ranged from 28 to 85 years,with median age of 59 years. The KRAS, NRAS, BRAF and PIK3CA gene mutations in the plasma and paired tumor specimens of all patients were detected by next generation sequencing. Results: The results of tissue samples test were gold standard. Comparison of the four genes showed that concordance rates between plasma and tissue samples were 81.1%(Kappa=0.543), 99.4%(Kappa=0.886), 99.4% (Kappa=0.886) and 97.7%(Kappa=0.714) respectively for KRAS, NRAS, BRAF and PIK3CA. The plasma detection rates of these genes were related to tumor stage(P=0.001), but not to gender(P=0.468) and age(P=1.000) of patients. Conclusions The study shows a high concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations in plasma against mutation status in tumor tissue. In colorectal cancer, tumor tissue remains the best specimen for gene detection. However, patients from tumor tissue specimens cannot be obtained, especially those with advanced metastases, plasma can be used instead of tissue to detect the mutation status of KRAS, NRAS, BRAF and PIK3CA to guide targeted therapy.

Objective:To investigate the incidence and treatment of gastric cancer in 16 medical centers in Tianjin from 2020 to 2021.Methods:The retrospective and descriptive study was conducted. The clinical data of 3 122 gastric cancer patients who underwent surgery in 16 medical centers, including Tianjin Medical University Cancer Institute & Hospital, et al, in Tianjin from 2020 to 2021 were collected. There were 2 112 males and 1 010 females, aged (64±11)years. Observation indicators: (1) general data of patients; (2) treatment situations; (3) postoperative complications. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were descri-bed as absolute numbers or percentages, and comparison between groups was conducted by the chi-square test. Results:(1) General data of patients. From 2020 to 2021, a total of 3 122 gastric cancer patients received surgeries in 16 medical centers in Tianjin, including 2 112 males and 1 010 females. There were 1 443 cases in 2020, including 976 males and 467 females, aged (63±11) years. There were 1 679 cases in 2021, including 1 136 males and 543 females, aged (65±11) years. Of the 3 122 pati-ents, cases in stage Ⅰ, Ⅱ, Ⅲ, Ⅳ were 696, 667, 1 466, 293, accounting for 22.293%(696/3 122), 21.365%(667/3 122), 46.957%(1 466/3 122), 9.385%(293/3 122), respectively. Cases with early gastric cancer, locally advanced gastric cancer, advanced gastric cancer account for 17.265%(539/3 122), 73.350%(2 290/3 122), 9.385%(293/3 122). There were 2 829 patients without distant metastasis and 293 patients with distant metastasis. For the 2 829 patients without distant metas-tasis, cases in stage T1, T2, T3, T4a, T4b accounted for 19.053%(539/2 829), 12.089%(342/2 829), 20.148%(570/2 829), 41.499%(1 174/2 829), 7.211%(204/2 829)respectively, cases in stage N0, N1, N2, N3 account for 37.328%(1 056/2 829), 16.331%(462/2 829), 15.836%(448/2 829), 30.505%(863/2 829). For the 293 advanced gastric cancer patients with distant metastasis, 190 cases had peri-toneal metastasis, 47 cases had lymph node metastasis, 27 cases had ovarian metastasis, 37 cases had liver metastasis, 14 cases had other metastasis (some patients had ≥2 distant metastases). (2) Treatment situations. ① For the 539 with early gastric cancer, cases undergoing endoscopic submu-cosal dissection, laparoscopic surgery, open surgery were 22, 150, 86 in 2020, versus 19, 212, 50 in 2021, showing a significant difference between them ( χ2=19.42, P<0.05). For the 498 patients with early gastric cancer who underwent laparoscopic or open surgery, cases undergoing open surgery including total gastrectomy, distal gastrectomy, proximal gastrectomy were 25, 81, 30, and cases undergoing laparoscopic surgery including total gastrectomy, distal gastrectomy, proximal gastrec-tomy were 18, 309, 35, respectively, showing a significant difference between them ( χ2=40.62, P<0.05). For the 2 290 patients with locally advanced gastric cancer, cases undergoing open surgery and laparoscopic surgery were 446 and 617 in 2020, versus 410 and 817 in 2021, showing a significant difference between them ( χ2=17.75, P<0.05). For the 2 290 patients with locally advanced gastric cancer, cases undergoing open surgery including total gastrectomy, distal gastrectomy, proxi-mal gastrectomy were 336, 377, 143, and cases undergoing laparoscopic surgery including total gastrectomy, distal gastrectomy, proximal gastrectomy were 377, 920, 137, respectively, showing a significant difference between them ( χ2=89.64, P<0.05). Of the 293 patients with advanced gastric cancer, 175 cases underwent surgeries due to hemorrhage, stenosis, perforation, 76 cases under-went surgery after chemotherapy, 42 cases underwent surgery directly. ② For 756 cases of 3 122 pati-ents undergoing total gastrectomy, 357 and 4 cases received open digestive tract reconstruction including Roux-en-Y and other anastomosis, versus 380 and 15 cases with laparoscopic digestive tract reconstruction including Roux-en-Y and other anastomosis, showing a significant difference between them ( χ2=5.57, P<0.05). For 1 687 cases undergoing distal gastrectomy, 84, 160, 158, 55 cases received open digestive tract reconstruction including Billroth Ⅰ anastomosis, Billroth Ⅱ + Braun anastomosis, Roux-en-Y anastomosis, uncut Roux-en-Y anastomosis, versus 154, 489, 417, 170 cases with laparoscopic digestive tract reconstruction including Billroth Ⅰ anastomosis, Billroth Ⅱ + Braun anastomosis, Roux-en-Y anastomosis, uncut Roux-en-Y anastomosis, showing a significant difference between them ( χ2=10.90, P<0.05) . Of the 539 patients with early gastric cancer, 65 cases had lymph node metastasis, in which 18 of 306 stage T1a cases had lymph node metastasis and 47 of 233 stage T1b cases had lymph node metastasis. The number of detected lymph nodes for the 2 290 patients with advanced gastric cancer was 31±15, including ≥16 for 2 059 cases and ≥30 for 1 276 cases. Of the 3 122 patients, cases with neoadjuvant therapy, complete response and incomplete response was 128, 13 and 115 in 2020, versus 250, 49 and 201 in 2021, showing a significant difference between them ( χ2=5.51, P<0.05). (3) Postoperative complications. Of the 3 122 patients, 746 cases had postoperative complications, with an incidence of 23.895%(746/3 122). There were 62 patients with grade 3 or more complications. Reoperation was conducted in 34 patients. There were 14 cases of postoperative death. The duration of postoperative hospital stay and hospital expense were (11±5)days and (98 114±46 598)yuan for the 3 122 patients, (26±14)days and (122 066±68 317)yuan for cases with complications, (40±21)days and (196 926±12 747)yuan for cases with grade 3 or more complications. Conclusion:Compared with 2020, cases undergoing laparoscopic surgery and distal gastrectomy for gastric cancer in Tianjin increases in 2021, and the digestive tract reconstruction also differs. The number of patients with neoadjuvant chemotherapy and complete response rate for advanced gastric cancer increases.

Objective: To understand the injuries among 16 459 left-behind children from 27 poor rural areas in 12 provinces of China, 2016. Methods: Data were collected from the survey of 'Health Service Needs Assessment’ (HSNA) program on left-behind children, from poor rural areas in the middle and western parts of China. Factors including causes, types, locations, related activities, ways of treatment and outcomes among left-behind children with injuries in 2016, were described and analyzed by gender and age groups. Results: In 2016, per-person and person-time incidence rates of injuries were 8.88% and 11.21%, among the 16 459 left-behind children from 27 poor rural areas in 12 provinces of China, both higher in boys, than in girls. Most injuries were unintentional with its proportion higher in older children. The main types of injuries were seen as falls, blunt and sharp injuries, with burns and animal injuries more common in younger children. Injuries among left-behind children mainly took place at home, kindergarten/school, and on the highways/streets/roads, during playing. Most common ways of treatment would include at the emergency settings, self-treated, with older children more likely to treat by themselves. Most injuries were cured. Conclusions In programs on prevention and control of injuries targeting the left-behind children in poor rural areas, special attention should be given to older boys, on falls and blunt/sharp injuries, at home or kindergarten/school. Education programs should pinpoint on self-rescue skills and guidance on kids by the parents, with behavioral norms and social support included. Related comprehensive prevention and control mechanism should be developed in families, schools and communities, with medical resources and insurance mechanism explored to serve these population and districts, including those left-behind children.

The four properties of Chinese herbal medicine have a history of several thousand years and are one of the important theoretical guides for the clinical application of Chinese herbal medicine. However， there have been few reviews of research methods and techniques for the four properties of Chinese herbal medicine in recent years. Therefore， this article summarized the advances and techniques for the four properties of Chinese herbal medicine by screening relevant literature on the four properties of Chinese herbal medicine and clarifying the characteristics， advantages， and applicable objects of each technique， in order to provide references for in-depth research on the four properties in the future. Chinese databases such as China national knowledge infrastructure （CNKI）， Wanfang data， and VIP， as well as international databases including PubMed， Cochrane Library， and EMbase were searched for relevant literature on the four properties of Chinese herbal medicine. The advances， research objects， and research techniques involved in the literature were extracted， classified， and summarized. Currently， the research techniques for the four properties of Chinese herbal medicine mainly include six categories， i.e.， literature data research， network pharmacology， biothermodynamics， cell biology， proteomics， and metabolomics. The research hierarchy can be divided into micro-level， small-level， medium-level， and macro-level. The research objects used in each experimental study are different， mainly single Chinese herbal medicine， Chinese herbal monomers， targets， microbial communities， cells， mice， and rats. Different research techniques explain the four properties of Chinese herbal medicine from different dimensions， which overall indicate the material basis of the four properties of Chinese herbal medicine. In future research， the interpretation of the four properties of Chinese herbal medicine can be first located at the research hierarchy， then corresponding research techniques can be selected according to the research hierarchy， and research indicators can be determined to obtain research conclusions. This can help researchers of traditional Chinese medicine effectively carry out research design and perform related experiments on the four properties of Chinese herbal medicine.

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality modulating the host response, pharmacokinetic herb-drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5'-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.