Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T＞C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective:To compare the efficacy of unilateral percutaneous kyphoplasty (PKP) and unilateral PKP combined with posterior medial branch block of the contralateral spinal nerve in the treatment of lumbar osteoporotic vertebral compression fracture (OVCF) in the elderly.Methods:A retrospective cohort study was conducted to analyze the clinical data of 161 aged patients with newly developed lumbar OVCF, admitted to Xi′an Central Hospital Affiliated to Xi′an Jiaotong University School of Medicine from January 2019 to January 2023, including 58 males and 103 females, aged 61-88 [(72.9±6.3)years]. All the patients were diagnosed with type II compression fracture based on acute symptomatic osteoporotic thoracolumbar fracture classification (ASOTLF). Seventy-eight patients underwent unilateral PKP (PKP group), while the other 83 patients underwent unilateral PKP combined with posterior medial branch block of the contralateral spinal nerve (PKP+contralateral block group). The operation time, intraoperative blood loss, and length of hospital stay were recorded. Beck index of the injured vertebra, Cobb angle of lumbar lordosis, Roland-Morris disability (RMD) score, visual analogue scale (VAS), and Oswestry disability index (ODI) were evaluated before operation, at 1 day, 1 week, 1 month, 3 months after operation, and at the last follow-up. The incidence of complications such as cement leakage was recorded as well.Results:All the patients were followed up for 6-8 months [(6.7±0.6)months]. There were no significant differences between the two groups in the operation time, intraoperative blood loss, or length of hospital stay ( P>0.05). The Beck index of the injured vertebra and Cobb angle of lumbar lordosis were not significantly different between the two groups before operation, at 1 day, 1 week, 1 month, 3 months after operation, and at the last follow-up ( P>0.05). The RMD score of the injured vertebra, VAS score, and ODI were not significantly different between the two groups before operation ( P>0.05). At 1 day, 1 week, 1 month, 3 months after operation, and at the last follow-up, the RMD scores in the PKP+contralateral block group were (11.23±1.05)points, (10.90±1.11)points, (10.10±1.06)points, (9.94±1.06)points, and (9.60±0.83)points respectively, which were all lower than (17.55±0.71)points, (15.78±0.86)points, (13.42±0.92)points, (10.67±0.78)points, and (9.78±0.72)points in the PKP group ( P<0.05 or 0.01); the VAS scores in the PKP+contralateral block group were (3.02±0.60)points, (2.96±0.55)points, (2.92±0.57)points, (2.88±0.61)points, and (2.70±0.51)points respectively, which were all lower than (3.60±0.57)points, (3.47±0.55)points, (3.32±0.46)points, (2.99±0.47)points, and (2.77±0.42)points in the PKP group ( P<0.05 or 0.01); the ODI values in the PKP+contralateral block group were 14.43±1.29, 14.54±1.24, 14.63±1.32, 14.37±1.31, and 13.42±1.45 respectively, which were all lower than 16.72±1.64, 16.09±1.49, 14.82±1.53, 14.74±1.46, and 13.69±1.75 in the PKP group ( P<0.05 or 0.01). The bone cement leakage rate was 12.0% (10/83) in the PKP+contralateral block group, similar to 11.5% (9/78) in the PKP group ( P>0.05). No other complications such as neurovascular injury, pulmonary embolism or adjacent vertebral fracture were found in either groups. Conclusion:In the treatment of lumbar OVCF in the elderly, unilateral PKP combined with posterior medial branch block of the contralateral spinal nerve is similar to unilateral PKP in terms of the operation time, intraoperative blood loss, length of hospital stay, effectiveness of reduction, and incidence of complications, but it can achieve better pain relief and more satisfactory functional recovery.

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.
Animals ; Mice ; Liver ; Aspartate Aminotransferases ; Bupleurum

Objective:To investigate the genomic manifestation and pathogenesis of osteosarcoma with different relapse pattens, which were respectively initially presented with bone metastasis or pulmonary metastasis.Methods:From May 1, 2021 to October 1, 2021, 38 fresh tumor specimens and some paraffin-embedded specimens of high-grade osteosarcoma were collected in Peking University People's Hospital, including 29 males and 9 females, aged 19.6±2.2 years (range, 6-61 years). Among the 38 cases, 12 cases had initial bone metastasis (group A) and 26 cases had initial lung metastasis (group B), of which 15 cases (40%, 15/38) had paired specimens of primary and metastatic lesions. Based on Illumina NovaSeq 6000, we analyzed whole-exome sequencing (WES) as well as transcriptome for osteosarcoma with paired samples in different relapse patterns. During all their treatment courses, we also collected their paired samples to reveal these tumors' evolution. We sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms.Results:We found that osteosarcoma in group A mainly carried single-nucleotide variations (83%, 10/12), displaying higher tumor mutation burden [4.9 (2.8, 12.0) & 2.4 (1.4, 4.5), P=0.010] and neoantigen load [743.0 (316.5, 1,034.5) & 128.5 (49.0, 200.5), P=0.003], while those in group B mainly exhibit structural variants (58%, 15/26). The mutation spectrum showed that there was a significant difference in age-related gene imprinting 1 between the bone metastasis group and the lung metastasis group ( P=0.005). Samples were randomly selected from group A (3 patients) to investigate immunologic landscape by multiplex immunohistochemistry, from which we noticed tertiary lymphatic structure from one patient from group A. High conservation of reported genetic sequencing over time was found in their evolving cladograms. Conclusion:Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases with older in age as well as better immunogenicity in tumor microenvironment.

Objective:To evaluate the medical service quality of psychiatric hospitals in Beijing based on diagnostic related group (DRG), analyze the evaluation effect, for refences to constructe a DRG performance evaluation system suitable for psychiatric hospitals.Methods:This study extracted data such as the number of DRG groups, etc. of hospitalized patients in 14 tertiary and secondary psychiatric hospitals in Beijing from 2018 to 2020 from the Beijing inpatient medical performance evaluation platform, and analyzed data on DRG performance evaluation indicators, as well as the average length of hospital stay and average cost of DRG enrolled cases. All data were analyzed using descriptive research methods, and inter group comparisons were conducted using the Mann Whitney U-test. Results:From 2018 to 2020, the average number of DRG groups in tertiary hospitals (28) was higher than that in secondary hospitals (10) ( P<0.05), and the average CMI values of both were the same(1.79); The average cost consumption index (1.15) of tertiary hospitals was higher than that of secondary hospitals (0.65) ( P<0.05), while the average time consumption index (1.11) was slightly lower than that of secondary hospitals (1.30); The mortality rate of the low-risk group in tertiary hospitals (0.01%) was generally lower than that in secondary hospitals (0.88%), and the average percentage of DRG admitted inpatients (82.8%) was significantly higher than that in secondary hospitals (27.3%) ( P>0.05). The average length of stay and cost per case for DRG enrolled inpatients in tertiary and secondary hospitals were lower than the overall hospital discharge cases ( P<0.05). Conclusions:The number of DRG groups, CMI value, and low-risk mortality rate could be used for evaluating the medical service capacity and safety of psychiatric hospitals, but the cost and time consumption index could not objectively reflect the efficiency of hospital medical services. DRG performance evaluation indicators are more suitable for evaluating short-term hospitalization of psychiatric patients. The proportion of DRG enrolled cases might be a potential indicator for evaluating the service quality of psychiatric hospitals.

The report presents a case with Enterobius vermicularis infections in Guiyang City, Guizhou Province, aiming to strengthen the attention to parasitic infections.

Objective: To examine the clinical effect of simple muscle packing through transnasal sphenoid approach in the treatment of intrasellar arachnoid cyst. Methods: The clinical data of 11 patients with intrasellar arachnoid cyst treated by transnasal sphenoidal approach with simple muscle packing at the Neurosurgery Department of the First Affiliated Hospital of Zhengzhou University from January 2014 to February 2020 were retrospectively analyzed. There were 5 males and 6 females, with a median age of 48 years (range: 23 to 75 years). The clinical manifestations included headache in 6 cases, dizziness in 4 cases, hypo-libido in 1 case, disturbance of consciousness in 1 case, visual impairment in 7 cases and mixed pituitary dysfunction in 5 cases. The enlargement of the sellar fossa was seen in the preoperative MRI images. The enhanced MRI images showed that the cyst wall of the intrasellar arachnoid cyst was not enhanced, and the compression and thinning of the sellar base was seen in the CT images. In 9 cases, the cyst extended suprasellar and the sellar septum was "arched". In 7 cases, the cyst compressed the optic chiasm upward. The cyst walls of all patients were incised through the nasal sphenoid approach under the endoscope, and the muscle was packed after sufficient drainage. The postoperative symptoms, pituitary endocrine function and recurrence of patients were followed up. Results: MRI images of the sellar region in all patients showed significant reduction or disappearance of cysts. Intracranial infection occurred in 1 case and electrolyte disorder in 2 cases, which were relieved after symptomatic treatment. No cerebrospinal fluid rhinorrhea occurred. Postoperative clinical symptoms were completely relieved in 6 cases and partially relieved in 5 cases. Pituitary endocrine function recovered completely in 2 cases and improved significantly in 4 cases. All patients were followed up for 10 to 40 months. One patient found to have a partial recurrence of the cyst 3 months after surgery. Because there were no new symptoms appeared, the follow-up was continued without second operation. Conclusion: Transnasal sphenoidal approach is a feasible method for the treatment of intrasellar arachnoid cyst.
Adult ; Aged ; Arachnoid Cysts/surgery* ; Endoscopy ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Muscles ; Retrospective Studies ; Sella Turcica ; Young Adult

Objective To investigate the prevalence and influencing factors of intestinal protozoan infections among rural children in Henan Province. Methods A total of 104 survey sites were sampled from 35 counties (cities) in Henan Province using the stratified cluster sampling method to investigate the prevalence of intestinal protozoan infections among rural children from 2014 to 2015. The trophozoites and cysts of intestinal protozoa were identified using the iodine staining method and the physiological saline direct smear method (one detection for one stool sample). The prevalence of intestinal protozoan infections was compared among rural children with different characteristics, and the factors affecting intestinal protozoan infections among rural children were identified. Results The overall prevalence of intestinal protozoan infections was 0.60% (40/6 771) among rural children in Henan Province from 2014 to 2015. There were 7 species of intestinal protozoa identified, and there was no species-specific prevalence (χ² = 37.732, P = 0.000). No significant differences were found in prevalence of intestinal protozoan infections among rural children in terms of gender (χ² = 1.793, P = 0.181), age (χ² = 1.443, P = 0.486), occupation (χ² = 0.219, P = 0.896) or ecological region (χ² = 1.700, P = 0.637). In addition, terrain (χ² = 2.311, P = 0.510), economic level (χ² = 4.322, P = 0.229), source of drinking water (χ² = 0.731, P = 0.393), eating raw vegetables (χ² = 1.134, P = 0.287) and deworming (χ² = 1.089, P = 0.297) had no remarkable effects on the prevalence of intestinal protozoan infections among rural children in Henan Province; however, the prevalence of intestinal protozoan infections varied significantly among rural children living in regions with different coverage of non-harmless toilets (χ² = 10.050, P = 0.018). Conclusion The prevalence of intestinal protozoan infections is low among rural children in Henan Province.