The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

OBJECTIVE: A prospective study was conducted to investigate the feasibility and effectiveness of three-dimensional printed in vitro guide plates assisted hip arthroscopy in the treatment of Cam-type femoroacetabular impingement (FAI). METHODS: The clinical data of 25 patients with Cam-type FAI who met the selection criteria between December 2016 and September 2022 were collected. There were 13 males and 12 females with an average age of 42 years (range, 19-66 years). The disease duration ranged from 3 to 120 months, with an average of 22.2 months. The preoperative range of internal rotation-external rotation was (28.70±4.50)°, α angle was (69.04±0.99)°, visual analogue scale (VAS) score was 6.5±0.2, and modified Harris hip score (HHS) was 50.5±0.7. All patients were treated with hip arthroscopy assisted by three-dimensional printed in vitro guide plate. The occurrence of complications was observed postoperatively, α angle of the affected hip joint was measured on Dunn X-ray film, and the glenoid labrum injury was observed by MRI. The percentage of overlap between the Cam plasty area and the preoperative simulated grinding area was calculated by three-dimensional CT+reconstruction. The effectiveness was evaluated by VAS score and modified HHS score. RESULTS: Postoperative dorsalis pedis numbness occurred in 1 case, and the symptoms disappeared after 1 month of conventional drug treatment such as neurotrophy. Two cases of perineal skin injury occurred, and healed after symptomatic treatment. There was no male erectile dysfunction, deep incision infection, pulmonary embolism, or other serious complications occurred. The percentage of overlap between the Cam plasty area and the preoperative simulated grinding area was 81.6%-95.3%, with an average of 89.8%. All 25 patients were followed up 6-12 months, with an average of 8 months. At last follow-up, the range of internal rotation-external rotation was (40.10±2.98)°, α angle was (43.72±0.84)°, VAS score was 1.8±0.2, and the modified HHS score was 72.1±1.3, which significantly improved when compared with preoperative ones ( P<0.05). CONCLUSION The treatment of Cam-type FAI with three-dimensional printed in vitro guide plates assisted hip arthroscopy is safe and feasible, and can achieve good effectiveness.
Humans ; Male ; Female ; Arthroscopy/methods* ; Middle Aged ; Adult ; Femoracetabular Impingement/surgery* ; Prospective Studies ; Printing, Three-Dimensional ; Aged ; Treatment Outcome ; Range of Motion, Articular ; Hip Joint/surgery* ; Young Adult ; Bone Plates

Objective:To evaluate the role of G-protein coupled receptor 37 (GPR37) in cognitive dysfunction in a mouse model of neuropathic pain.Methods:SPF-grade healthy male C57BL/6 mice and GPR37 knockout (GPR37-KO) mice, aged 3 months, with a body weight of approximately 20 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (Con group), neuropathic pain group (NPP group), GPR37-KO+ control group (GPR37-KO Con group) and GPR37-KO+ neuropathic pain group (GPR37-KO NPP group). The mouse model of neuropathic pain was established by ligation of the sciatic nerve. The thermal paw withdrawal latency (TWL) and mechanical paw withdrawal threshold (MWT) were measured at 7 days after surgery. The open field test and Morris water maze test were performed at 28 days after surgery. The mice were subsequently sacrificed, and the medial prefrontal cortex (mPFC) was obtained for determination of the level of phosphorylated calcium/calmodulin-dependent protein kinase Ⅱ(p-CAMKⅡ) and expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95). Results:Compared to Con group, no significant changes were found in the parameters in GPR37-KO Con group ( P>0.05), and TWL was significantly shortened, MWT was decreased, the time the animal spent in central area was prolonged and the platform-crossing times were increased in the open field test, and the escape latency was prolonged and platform-crossing times were decreased in the Morris water maze test, and the expression of p-CAMKⅡ, BDNF and PSD-95 in the mPFC was down-regulated in NPP group ( P<0.05). Compared with NPP group, TWL was significantly shortened, MWT was decreased, the time the animal spent in central area was prolonged and the platform-crossing times were increased in the open field test, and the escape latency was prolonged and platform-crossing times were decreased in the Morris water maze test, and the expression of p-CAMKⅡ, BDNF and PSD-95 in the mPFC was down-regulated in GPR37-KO NPP group ( P<0.05). Conclusions:GPR37 is involved in the development of cognitive dysfunction in mice with neuropathic pain, and the mechanism may be related to its modulation of synaptic plasticity.

Objective: To investigate the anti-tumor effect of CTL cells on colon cancer xenograft in nude mice after knocking out the immune check point CTLA-4 by CRISPR/Cas9 technology. Methods: A specific small guide RNA (sgRNA) for CTLA-4 was designed to construct sgRNA/Cas9 plasmid, which was then transfected into CTL using a lentiviral vector to obtain CTL cells with CTLA-4 deletion (CTLA-4 KO CTL). The transfection efficiency of the plasmid and the deletion efficiency of CTLA-4 were verified. BALB/c nude mice were randomly divided into two groups to prophylactically inoculate CTLA-4 KO CTL (experimental group) or CTL (control group); 3 days later, the animals of two groups were inoculated with colon cancer cell line LS174-T to observe the tumor formation rate and tumor formation time. After constructing colon cancer xenograft model in nude mice, the animals were randomly divided into two groups, respectively treated with CTLA-4 KO CTL (experimental group) and CTL (control group) cells to observe the tumor growth volume and survival time of mice. The serum levels of TNF-α and IFN-γ in nude mice were detected. Results: sgRNAwas designed and CRSIPR/Cas9 system with lentivirus as vector was successfully constructed. CTL cells were transfected with the established CRSIPR/ Cas9 system, and the highest transfection efficiency was up to (28.80±0.62)%. After transfection, the deletion efficiency of CTLA-4 was detected by Flow cytometry. The CTLA-4 expression of CTLA-4 KO CTL group was significantly lower than that of CTL group [(0.91±0.25)% vs (42.70±2.72)%, P<0.05]. In prophylactic assay, the formation rate of colon cancer xenografts in the experimental group was significantly lower than that in the control group(33.33%vs100%,P<0.05). In treatment assay, the tumor volume in the experimental group was significantly inhibited compared with the control group ([503±23.9] vs [911.2±51.4] mm3, P<0.05), and the survivaltimeoftheexperimentalgroupwassignificantlyprolonged (mediansurvivaltime:78dvs42d,P<0.05); Moreover, the secretion levels of serumTNF-α([268.93±17.04]pg/mlvs[148.26±20.07]pg/ml,P<0.05) and IFN-γ(315.38±18.67 pg/ml vs 202.92±29.32 pg/ml, P<0.05) in the experimental group were significantly higher than those in the control group. Conclusions: The lentiviral vector CRSIPR/Cas9 system is an effective gene editing method; its successful deletion of CTLA-4 in CTL cells can significantly inhibit the tumor formation rate of colon cancer xenografts in nude mice and enhance the anti-tumor effect of CTLon colon cancer xenografts.

OBJECTIVETo investigate the safety and clinical significance of pelvic floor reconstruction in extralevator abdominoperineal excision(ELAPE) for advanced low rectal cancer.

METHODSThe clinical efficacy was retrospectively analyzed in 30 patients with low rectal cancer who underwent ELAPE from January 2013 to December 2016 in Nanjing Drum Tower Hospital, the affiliated Hospital of Nanjing University Medical School. There were 21 male patients and 9 female, with an average age of 61.7 years old. We used 13*15 cm Biodesign biologic meshes(Cook, China) for the reconstruction and the procedure involved soaking in saline solution for 5 minutes and fixation of the mesh to the cut edges of the levators by non-absorbable 2-0 sutures. A perineal drain was used and was removed when drainage was minimal. Potassium permanganate was used for hip bath after removing the stitches. The surgical procedure, postoperative complications, prognosis and follow-up of all these patients were documented.

RESULTSThe operations of all patients were completed successfully. ELAPE could remove more para cancer tissues in the distant rectum. There was no rectum perforation, and the circumferential resection margins of all specimens were proved to be negative. During the follow-up of 21 months, only 2 patients suffered incision infection and healed uneventfully after strengthening the dressing. No one developed perineal breakdown, bulge or intestinal obstruction, as well as local recurrence and pelvic floor hernia. There was also no complication related to mesh. The average hospitalization time was 10 days (9-15 days).

CONCLUSIONSThe ELAPE could render a low occurrence of intraoperative perforations and circumferential resection margins. Reconstruction of pelvic floor with biologic meshmight lower the complication incidences associated with the perineal region.

Objective To analyze the correlative factors of hypopituitarism in patients with intracranial non-sellar tumors.Methods Eighty-three patients with intracranial non-sellar tumors,admitted to our hospital from May 2014 to April 2015,were included in our study;their clinical data were retrospectively analyzed.The status of pituitary function was assessed according to the level of preoperative serum hormone.Univariate and multivariate Logistic regression analyses were employed to analyze the correlations of preoperative hypopituitarism with age,gender,hypertension,epilepsy history,course of disease,mass effect of tumor,tumor location,intracranial pressure (ICP),and composition of cerebrospinal fluid.Results Before surgery,30 showed hypopituitarism,accounting for 36.14％:23 had deficiency in one pituitary axe and 7 had multi-axial deficiency.Univariate analysis showed that high ICP (ICP＞200 mmH2O),acute or sub-acute course (≤ 3 months) and presence of mass effect by non-sellar brain tumor were the risk factors of hypopituitarism (P＜0.05).Multivariate Logistic regression analysis revealed that intracranial mass effect in patients with non-sellar brain tumor was an independent risk factor (OR=3.197,95％CI=1.085-9.423,P=0.035).Conclusion Hypopituitarism has high morbidity in patients with non-sellar brain tumor;intracranial mass effect is an independent risk factor for hypopituitarism.

Objective To study the molecular mechanism of Bel subtype caused by mutation p.R168W of glycosyltransferase B.Methods Serological test,SSP-PCR and direct sequence the Exon6 and Exon 7 of the ABO gene.Construct a 3D molecular model and predict the structural impact of GTB protein mutations.Results A antigen or B antigen can't be detected on the surface of the propositus' RBC,and only anti-A antibodies were detected in her serum.But serological test indicated her daughter's blood type was a normal B type.SSP-PCR test indicated propositus' ABO gene type is O1 B.By gene sequencing the Exon 6 and Exon 7 of the ABO gene,a ABO Bel allel(c.502C＞T,p.R168W)was discoverd in both the propositus and her daughter.Through the propositus' daughter coexisted Bel gene with normal B gene,her blood type was a normal B type.Conclusions ABO gene c.502C＞T mutations cause Bel phenotypes in patients by reducing the stability of GTB.

Objective To investigate the accuracy of volumetric measurements (Dotian formula and platform-like volume calculation formula [PLVCA]) in pituitary adenomas and their practicabilities.Methods Forty-five large and giant pituitary adenomas patients,admitted to our hospital from May 2013 to May 2014,were collected.According to the imaging finds of pituitary adenomas,the patients were divided into regular type group and irregular type group;the volume of these tumors were calculated by PLVCA method,Dotian formula and virtual reality (VR) reconstruction method,respectively.The results of VR method were used as the standards to investigate the accuracy of Dotian formula and PLVCA method on pituitary adenomas.Results In 45 pituitary adenomas,17 (37.78％) were regular;the result of tumor volume using VR method was (6.54±11.27) cm3,that using PLVCA method was (5.50±9.40) cm3 and that using Dotian formula was (4.32±9.00) cm3;significant differences were noted between the results of VR method and PLVCA method and the results of VR method and Dotian formula (P＜0.05);there was no significant difference between the results of PLVCA method and Dotian formula (P＞0.05).Another 28 (62.22％) were irregular;the result of volume using VR method was (11.65±16.60) cm3,that using PLVCA method was (11.50±16.18) cm3,there was no significant difference between the two results (P＞0.05);that using Dorian formula was (10.04±19.45) cm3,and there was significant difference between the VR method and Dotan formula (P＜0.05),which was also found between PLVCA method and Tada formula (P＜0.05).Conclusion PLVCA method has a higher accuracy in volume measurement of pituitary adenomas than Dotian formula,especially in irregular adenomas.

OBJECTIVETo study the clinicopathological features and prognosis of multifocal gastric cancer.

METHODSClinicopathological data of 30 cases with multifocal gastric cancer from January 2003 to March 2014 in our department were retrospectively analyzed. Random selection of 100 cases of single focal gastric cancer patients admitted in the same period was used as control group. Clinicopathological features and prognosis were compared between two groups.

RESULTSSix(20.0%) multifocal gastric cancer patients had 3 or more focuses with different differentiation degrees at the same time. The age of multifocal gastric cancer patients was younger than that of single focal gastric cancer [(56.8±16.4) year vs. (63.3±10.8) year, P<0.05]. The TNM stage of multifocal gastric cancer was mainly stage I((73.3%, 22/30), and the TNM stage of single focal gastric cancer was mainly stage III((64.0%, 64/100). As compared to single focal gastric cancer group, multifocal gastric cancer group had smaller tumors, lower ratio of nerve invasion and lymphatic vascular invasion(all P<0.01). Five-year survival rate was higher in multifocal gastric cancer group as compared to single focal gastric cancer group(76.0% vs. 48.8%, P<0.05). The prognosis of multifocal gastric cancer patients was associated with tumor size, nerve invasion, vascular invasion, depth of tumor invasion, lymphatic metastasis and TNM staging(all P<0.05), which was similar to single focal gastric cancer patients. Differences of 5-year survival rate under various clinicopathological conditions were not significant between two groups(all P>0.05).

CONCLUSIONMultifocal gastric cancer patients have earlier staging tumor and overall advantage as compared to those with single focal gastric cancer.

Objective To study the clinicopathological features and prognosis of multifocal gastric cancer. Methods Clinicopathological data of 30 cases with multifocal gastric cancer from January 2003 to March 2014 in our department were retrospectively analyzed. Random selection of 100 cases of single focal gastric cancer patients admitted in the same period was used as control group. Clinicopathological features and prognosis were compared between two groups. Results Six(20.0%) multifocal gastric cancer patients had 3 or more focuses with different differentiation degrees at the same time. The age of multifocal gastric cancer patients was younger than that of single focal gastric cancer [(56.8±16.4) year vs. (63.3±10.8) year, P<0.05]. The TNM stage of multifocal gastric cancer was mainly stageⅠ(73.3%, 22/30), and the TNM stage of single focal gastric cancer was mainly stage Ⅲ (64.0%, 64/100). As compared to single focal gastric cancer group, multifocal gastric cancer group had smaller tumors, lower ratio of nerve invasion and lymphatic vascular invasion (all P<0.01). Five-year survival rate was higher in multifocal gastric cancer group as compared to single focal gastric cancer group (76.0% vs. 48.8%, P<0.05). The prognosis of multifocal gastric cancer patients was associated with tumor size, nerve invasion, vascular invasion, depth of tumor invasion, lymphatic metastasis and TNM staging (all P<0.05), which was similar to single focal gastric cancer patients. Differences of 5-year survival rate under various clinicopathological conditions were not significant between two groups (all P>0.05). Conclusion Multifocal gastric cancer patients have earlier staging tumor and overall advantage as compared to those with single focal gastric cancer.