This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

ObjectiveTo investigate the changes in the pathogen spectrum of viral diarrhea in local pediatric inpatients as well as any variations in genotypes of major pathogens during the COVID-19 control period. MethodsFecal samples were collected from the children <5 years who were hospitalized due to acute gastroenteritis in a pediatric hospital in Shanghai. PCR test was carried out to detect rotavirus， norovirus， sapovirus， astrovirus and enteric adenovirus， and then genotyping was performed for major pathogens. ResultsOut of 546 samples， 37.55% tested positive for virus with the following positive rate ranking： norovirus GⅡ （22.16%）， group A rotavirus （16.12%）， astrovirus （2.93%）， enteric adenovirus （2.38%）， sapovirus （0.92%） and norovirus GⅠ （0.18%）. The predominant genotype within norovirus GⅡ were GⅡ.4［P31］ and GⅡ.4［P16］ with a proportion of 24.79% and 14.05% respectively. The detection rate of GⅡ.4［P31］ dropped significantly over the 2-year period （χ²＝16.140，P<0.001）. In addition， an emerging rotavirus genotype G8P ［8］， which was rarely found nationally， was discovered for the first time locally with an increasing proportion， accounting for 7.95% of all rotavirus positive cases. Phylogenic analysis demonstrated that the representative strains of this genotype were genetically closer to the DS-1-like G8P ［8］ strain found in Southeast Asia. ConclusionThe changes in the prevalence of various norovirus genotypes together with the emergence of rare rotavirus genotype in the local area illustrate the importance of continuous monitoring of viral diarrhea and genotyping of key pathogens. Increased local activity of the rare genotype also adds new parameters in the efficacy evaluation of marketed vaccines and development of potential new vaccines in near future.

Objective: To analyze the disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019, so as to provide the basis for prevention and control of colorectal cancer. Methods: Based on data of 2019 Global Burden of Disease (GDB 2019), disease burden and risk factors of colorectal cancer in Zhejiang Province from 1990 to 2019 was assessed using years of life lost (YLL), years lived with disability (YLD), disability-adjusted life years (DALY). Results: In 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province were 496.15/105, 31.81/105 and 527.96/105, respectively. From 1990 to 2019, the YLL rate, YLD rate and DALY rate caused by colorectal cancer in Zhejiang Province increased by 114.90%, 482.60% and 123.38%, respectively, showing increasing trends (average annual percent change values were =2.663, 6.283 and 2.800, respectively,all P<0.05). From 1990 to 2019, the YLL rate, YLD rate and DALY rate in the age groups of 15 to 49 years, 50 to 69 years and 70 years and older showed increasing trends (all P<0.05). In 1990, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in calcium, diet low in milk, diet low in whole grains, smoking, alcohol use, low physical activity, high fasting plasma glucose, diet high in red meat, diet low in fiber and high body mass index. In 2019, the top ten risk factors for colorectal cancer in Zhejiang Province were diet low in milk, diet low in whole grains, diet low in calcium, alcohol use, diet high in red meat, high body mass index, high fasting plasma glucose, low physical activity, diet low in fiber and diet high in processed meat. Conclusions The disease burden of colorectal cancer in Zhejiang Province showed an upward trend from 1990 to 2019. The top ten risk factors for colorectal cancer remained between 1990 and 2019, while there was a slight change in ranking.

Objective To investigate the effect of the socket-shield technique(SST)concurrent with immediate im-plant placement and provisionalization(IIPP)in the aesthetic restoration of anterior teeth.Methods A case of maxil-lary anterior tooth stumps with a thin labial bone wall was treated with SST for preservation of labial soft and hard tissue fullness,combined with an immediate implant placement and immediate provisional crown for restoring the shape of the tooth and gingival molding.Results Immediate implant placement and provisionalization restored the morphology and function of the affected tooth in the shortest possible time.The patient's labial soft and hard tissue contours in the affected tooth area were well preserved in the 18-month follow-up after the application of the SST,which presented a better aesthetic result.The literature review indicates that the indications for SST are unrestorable maxillary anterior teeth,whose dental,periodontal and periapical tissues are healthy and intact.In the esthetic zone,root shielding is effec-tive in maintaining the soft and hard tissue contour on the labial side of the implant.However,there is no consensus on the technical details of SST,such as the ideal coronal height and thickness of the shield,and the management of the gap between the shield and the implant.Thus,more clinical studies and histologic evidence are needed to provide a refer-ence for clinical decision-making.In addition,digital technology can improve the accuracy of implant placement and shield preparation.Conclusion The correct application of SST combined with IIPP in the esthetic zone can ensure es-thetic results.However,more high-quality evidence-based medical evidence is needed for its long-term efficacy,and in-dications should be strictly controlled during clinical application.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

Objective To observe the clinical efficacy and adverse drug reactions of recombinant human growth hormone on dwarfism in children with primary nephrotic syndrome.Methods Children with dwarfism in primary nephrotic syndrome were divided into control group and treatment group.Patients in control group were orally administered prednisone acetate tablets,with an initial dose of 2 mg·kg-1·d-1,at once,no more than 60 mg in a single day,and after a duration of 6 weeks of full dosage,the dosage was reduced by 2.5 mg every 2 weeks until the maintenance dose of 5-10 mg·d-1 was administered for 12 months.Patients in treatment group were injected subcutaneously with recombinant human growth hormone 0.15 U·kg-1 at 0.5 h before bedtime every night on the basis of control group for a period of 12 months.The levels of height,bone age,standard deviation fraction of height(HtSDS),insulin-like serum growth factor 1(IGF-1),insulin-like growth factor binding protein 3(IGFBP-3),and the incidence of adverse drug reactions were compared between the two groups.Results There were 63 cases in control group and 63 cases in treatment group.The height of the children in treatment group and control group after treatment were(146.48±6.76)and(138.62±4.95)cm;the HtSDS values were-1.72±0.18 and-1.97±0.20;the IGF-1 values were(158.86±18.24)and(113.14±15.88)ng·mL-1;IGFBP-3 values were(5.21±0.83)and(3.13±0.71)μg·mL-1,the differences were all statistically significant(all P＜0.05).The incidence of adverse drug reaction in treatment group and control group were 9.52％(6 cases/63 cases)and 3.17％(2 cases/63 cases),with no statistically significant difference(P＞0.05).Conclusion Recombinant human growth hormone has a definite clinical efficacy,high safety,and effective promotion of growth and development in the treatment of primary nephrotic syndrome in children with dwarfism.

Objective To observe the application effect of intra-arterial tirofiban during mechanical thrombectomy for acute anterior circulation cerebral infarction.Methods The clinical data of patients with acute anterior circulation cerebral infarction were retrospectively analyzed.According to cohort method,they were divided into control group and treatment group.The control group was treated with mechanical thrombectomy,while the treatment group was additionally given intra-arterial therapy with tirofiban 0.25-0.5 mg on the basis of the control group.The perioperative indicators(surgical time,number of thrombectomy,vascular recanalization time,vascular recanalization rate),National Institutes of Health Stroke Scale(NIHSS)score before treatment and at 24 hours and 7 days after treatment,platelet indicators[mean platelet distribution width(PDW),mean platelet volume(MPV),plateletcrit(PCT)],hemorheological indicators[plasma viscosity(PV),low whole blood viscosity(LWBV),high whole blood viscosity(HWBV)],serum indicators[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),vascular endothelial growth factor(VEGF)]and clinical efficacy were compared,and the safety of the treatment regimen was assessed.Results There were 92 patients were finally included in this study,including 49 cases in control group and 43 cases in treatment group.The effective rates in treatment group and control group were 75.51％(37 cases/49 cases)and 93.02％(40 cases/43 cases),with significant difference(P＜0.05).The surgical times in treatment group and control group were(93.53±9.86)and(91.59±8.36)min;the vascular recanalization times were(78.46±9.69)and(77.40±10.32)min;the vascular recanalization rates were 93.02％and 83.67％;the NIHSS scores were(10.32±2.90)and(9.59±2.84)points at 24 hours after treatment,all with no significant difference(all P＞0.05).At 7 days after treatment,the NIHSS scores in treatment group and control group were(3.34±1.25)and(4.12±1.48)points;the PDW values were(12.58±1.81)％and(14.15±1.95)％;MPV values were(9.16±1.24)and(11.26±1.86)fL;PCT levels were(0.33±0.05)％and(0.29±0.04)％;PV values were(1.64±0.27)and(1.99±0.24)mPa·s-1;LWBV values were(4.16±0.48)and(5.01±0.49)mPa·s-1;HWBV values were(8.12±0.54)and(9.27±0.68)mPa·s-1;serum hs-CRP levels were(3.57±0.45)and(4.48±0.83)mg·L-1;TNF-α levels were(20.42±4.55)and(27.34±4.95)ng·L-1;VEGF levels were(738.80±52.41)and(664.72±41.68)ng·L-1,all with significant difference(all P＜0.05).Incidence rates of adverse drug reactions in treatment group and control group were 8.16％(4 cases/49 cases)and 4.65％(2 cases/43 cases)respectively,with no significant difference(P＞0.05).Conclusion Intra-arterial tirofiban therapy during thrombectomy for acute anterior circulation cerebral infarction has good neurological function and prognosis,and it may be related to the improvement of platelet function and cerebral tissue blood flow and relief of inflammatory response.

Objective To investigate the inhibitory effect of farrerol on inflammation and abnormal muscle tone of cerebral basilar artery in mice induced by high salt and its molecular mechanism based on the Janus kinase 2(JAK2)/Transcription activator 3(STAT3)pathway.Methods A total of fifty C57BL/6J mice were randomly divided into normal group(normal feeding),model group(high salt diet),experimental-L group(high salt diet+oral administration of 12.5 mg·kg-1·d-1 farrerol),experimental-M group(high salt diet+oral administration of 25 mg·kg-1·d-1 farrerol)and experimental-H group(high salt diet+oral administration of 50 mg·kg-1·d-1 farrerol).The model was prepared for 12 weeks.The contractile response of the cerebral basilar artery of mice in each group to vasoconstrictor was recorded with myographs.Enzyme linked immunosorbent assay(ELISA)were used to detect the levels of inflammatory factor.The protein expression levels of JAK2/STAT3 pathway related proteins were detected by Western blot.Results In the normal group,model group,experimental-L group,experimental-M group,experimental-H group,the contraction effects of the cerebral basilar artery to 60 mmol·L-1 potassium chloride(KCl)were(2.19±0.13),(2.66±0.11),(2.52±0.09),(2.41±0.08)and(2.25±0.10)mN;the contraction effects to 10-5 mol·L-1 vasopressiu(AVP)were(1.98±0.09),(2.46±0.08),(2.33±0.12),(2.11±0.10)and(2.05±0.06)mN;the contraction effects to 2.5 mmol·L-1 calcium chloride(CaCl2)were(1.77±0.08),(2.09±0.09),(2.03±0.08),(1.94±0.05)and(1.86±0.06)mN;in the serum,the levels of interleukin(IL)-1β were(10.10±3.21),(47.28±4.78),(40.16±3.98),(35.87±4.12)and(20.32±3.17)pg·mL-1;the levels of tumor necrosis factor-α(TNF-α)were(60.26±5.43),(134.32±4.15),(110.65±3.56),(90.79±5.25)and(81.54±6.23)pg·mL-1;the levels of chemokine ligand 3(CCL3)were(68.93±4.16),(146.37±5.73),(128.29±4.38),(100.25±6.82)and(84.16±3.89)pg·mL-1;the protein expression levels of JAK2 were 0.52±0.05,1.28±0.07,1.11±0.06,0.88±0.09 and 0.75±0.04;the protein expression levels of STAT3 were 0.58±0.07,1.93±0.10,1.62±0.04,1.34±0.06 and 0.88±0.09,respectively.The above indicators in the model group were significantly higher than the normal group(all P＜0.01);compared to the model group,the above indicators in the experimental-M and-H groups were significantly reduced(P＜0.05,P＜0.01).Conclusion Farrerol maybe improve the inflammation and abnormal muscle tone of cerebral basilar artery in mice induced by high salt by downregulating JAK2/STAT3 pathway.

Objective To investigate the mechanism of melezitose(MELE)on ulcerative colitis(UC)by structing a mouse model of ulcerative colitis(UC)induced by dextran sodium sulfate(DSS).Methods Forty-eight SPF grade male c57BL/6 mice were randomly divided into normal group(0.9％NaCl),model group(0.9％NaCl),control group(100 mg·kg-1 mesalazine)and experimental-L,-M,-H groups(20,40,80 mg·kg-1 melezitose solution).The UC model was induced by giving 3％DSS solution instead of drinking water,and the disease activity index(DAI)was evaluated.Serum levels of interleukin-1 β(IL-113),IL-6,IL-10 and tumor necrosis factor α(TNF-α)were detected by enzyme linked immunosorbent assay.The expression levels of major histocompatibility complex Ⅱ(MHC Ⅱ)and cluster of differentiation 4 receptors(CD4)protein were detected by Western blot.Results The levels of IL-1 β in serum in the experimental-M,-H groups,model group and normal group were(82.15±13.66),(75.56±11.07),(118.20±19.31)and(23.47±4.72)pg·mL-1;serum IL-6 levels were(71.54±16.48),(58.57±15.62),(140.60±5.76)and(30.33±4.15)pg·mL-1;serum IL-10 levels were(48.64±5.60),(52.65±7.99),(27.10±4.91)and(61.90±10.44)pg·mL-1;serum TNF-α levels were(70.33±8.51),(66.55±8.12),(90.88±4.90)and(34.18±4.15)pg·mL-1;the relative expression levels of MHC Ⅱ protein were 0.34±0.04,0.15±0.06,0.08±0.05 and 0.53±0.59;the relative expression levels of CD4 protein were 0.79±0.08,0.92±0.12,0.99±0.11 and 0.54±0.14,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups showed statistically significant differences(P＜0.05,P＜0.01).Conclusion Melezitose could effectively improve the symptoms of UC mice;the mechanism may be through down-regulating MHC Ⅱ protein and up-regulating CD4 protein to activate T cell signal pathway to play an anti-inflammatory effect.