[Clinicopathological analysis of gonadal differentiation of sex development disorder].

Objective: To investigate pathological features and differential diagnosis in the gonads with disorder of sex development. Methods: Thirty-six cases of clinically diagnosed hermaphroditism with gonadal biopsy in the Department of Pathology, the Seventh Medical Center of People's Liberation Army General Hospital from April 2007 to July 2021, were collected. All biopsy pathological sections were reviewed, and the gonadal cases with abnormal pathological morphology were screened out. The clinical and imaging data and karyotype of these cases were reviewed. Additional immunohistochemical staining was performed and relevant literature was reviewed. Results: Seven cases of ovotesticular disorder of sex development (OTDSD) were identified, which were characterized by the presence of testicular and ovarian differentiation in the same individual. All patients were under 15 years old and presented with abnormal appearance of external genitalia, and the ratio of male to female was 2∶5. Ultrasonography showed testicular structure in all female patients and cryptorchidism in all male patients. The most common karyotype was 46, XX. One case with undifferentiated gonadal tissue (UGT) and one case with streak gonads were screened out. UGT germ cells were neither in seminiferous tubules nor in follicles, but randomly distributed in an ovarial-type interstitial background, sometimes accompanied by immature sex cords. Streak gonads resembled UGT without germ cells. FOXL2 was positive in granulosa cells, but negative in Sertoli cells. SOX9 expression was opposite. OCT4 was weakly positively/negatively expressed in oocytes and positively expressed in the germ nuclei of UGT. Conclusions: Four differentiation patterns need to be identified in the gonadal biopsy: ovarian differentiation, testicular differentiation, undifferentiated gonadal tissue and streak gonad. The positive expression of SOX9 indicates testicular differentiation, while the positive expression of FOXL2 confirms ovarian differentiation, and the expression of both markers in the same tissue indicates ovotestis differentiation. It is very important to identify UGT, because that has a high probability of developing into gonadoblastoma in the future.

[Prognostic significance of immunoparesis in newly diagnosed multiple myeloma patients who achieved deep response].

Objective: To evaluate the effect of immune status on disease progression in patients with newly diagnosed multiple myeloma (NDMM) achieving deep response. Methods: Clinical data of 125 NDMM patients at Beijing Chaoyang Hospital from August 2015 to February 2020 were retrospectively analyzed who achieved very good partial response (VGPR) or better after front-line treatment. The immune status and its influence on progression-free survival (PFS) were analyzed. Results: (1) All patients received novel drug regimens, and 50.4% (63/125) patients followed by autologous stem cell transplantation (ASCT). The rate of complete response (CR) as best efficacy was 89.6%, in which 66.4% achieved CR and MRD negativity tested by second generation flow cytometry. (2) Cox multivariate analysis suggested that persistent severe immunoparesis 3 months and 6 months since the best response was an independent poor prognostic factor for PFS. (3) The 3-year PFS rate in the severe immunoparesis group was significantly lower than that in the control group (41.3% vs. 64.4%, P=0.021). (4) The 3-year PFS rates in patients with persistent severe immunoparesis at 3 months or 6 months were significantly lower (30.0% vs. 63.5%, P<0.001; 16.4% vs. 63.8%, P<0.001 respectively). (5) Even in those achieving CR and negative MRD, the 3-year PFS rate when severe immunoparesis lasted 6 months was significantly lower (22.2% vs. 83.2%, P=0.005). Conclusion: The immune status in NDMM patients achieving deep response is closely related to survival. Persistent severe immunoparesis indicates early progression of the disease.

[The prognostic value of dynamic minimal residual disease after autologous hematopoietic stem cell transplantation in patients with multiple myeloma in novel-agent era].

Objective: To investigate the clinical prognostic value of dynamic minimal residual disease (MRD) after autologous hematopoietic stem cell transplantation (AHSCT) in patients with multiple myeloma (MM). Methods: Patients with MM who underwent AHSCT in Beijing Chao-Yang Hospital from February 2016 to December 2019 were enrolled in this study. All the patients in the study had complete baseline data at the diagnosis. AHSCT was performed after induction chemotherapy. Response evaluation was performed after induction therapy. All the patients were assessed at approximately 100 days after AHSCT. Bone marrow MRD by NGF was performed every three months and dynamically monitored for at least 12 months. All the patients were divided into different groups according to cytogenetics and MRD status. Survivals in different groups were analyzed by IBM SPSS 22.0 statistical software. Results: A total of 150 patients with MM were enrolled in this study at last, including 66 patients in the cytogenetic standard risk group and 84 patients in the cytogenetic high-risk group. The median age was 54 years (range 30-68 years) and 87 male patients (58.0%) was in the study. The median follow-up was 36 months (range 16-72 months). Patients in the standard-risk group had better clinical prognosis than those in the high-risk group [median PFS in the standard-risk group was not achieved, and median PFS in the high-risk group was 45 months (P<0.001); median OS of both groups was not reached, and the estimated 3-year OS rate of the standard-risk group and the high-risk group was 95.2% and 78.9%, respectively (P=0.001)]. According to MRD status of patients, patients in each group were divided into three subgroups: persistent positive (Ppos), transient negative (Tneg) and persistent negative (Pneg). The median OS and median PFS of all subgroups in the standard-risk group was not reached (P=0.324 and P=0.086). In high-risk group, the median OS of MRD Pneg subgroup was not reached, and the estimated 3-year OS rate was 100%; The median OS of MRD Ppos subgroup was 52 months, and MRD Tneg subgroup only 31 months (P=0.002); the median PFS of MRD Pneg group was not reached, and the estimated 3-year PFS rate was 85.4%; median PFS of MRD Ppos subgroup was 40 months, and MRD Tneg subgroup only 17 months (P=0.001). Conclusions: MRD Pneg might overcome the adverse prognosis of MM patients with high-risk cytogenetics. However, MRD Tneg might be a poor prognostic factor for the patients with cytogenetic high-risk MM.

[Expression of PD-L1 and tumor infiltrating lymphocyte markers in uterine cervical carcinoma].

Objective: To investigate the expression of PD-L1, CD4, CD8 and CXCL-13 in cervical carcinoma, and their clinicopathological significance was analyzed. Methods: A total of 77 patients with cervical carcinoma in the Seventh Medical Center, PLA General Hospital from January 2019 to December 2021 were included. All patients received radical surgical resection in the Seventh Medical Center of Chinese PLA General Hospital. The expression of PD-L1, CD4, CD8 and CXCL-13 was detected by immunohistochemical (IHC) method. The correlation between IHC markers and patients' clinicopathological parameters was analyzed. Results: There were 59 cases of squamous cell carcinoma and 18 cases of adenocarcinoma (ranging from 29 to 69 years) with an average of (49.4±9.8) years. PD-L1 was expressed in different degrees in cervical squamous cell carcinoma and adenocarcinoma (χ²=4.975, P=0.026); CD4+, CD8+and CXCL-13+tumor infiltrating lymphocytes (TIL) were observed in the carcinoma cell nests and peritumoral stroma. PD-L1 expression in cervical carcinoma was moderately correlated with the number of CD4+TIL in the carcinoma nests, and the number of CD8+, CXCL-13+TIL infiltration in the carcinoma nests and stroma, but not to the patient's age, histologic differentiation, presence or absence of vascular invasion, presence or absence of lymph node metastasis and FIGO stage (P>0.05). Conclusions: The high expression of PD-L1 in cervical carcinoma tissues is closely related to the number of TIL in the carcinoma nests and peritumor stroma, suggesting that they may have important reference value for predicting the response to immunotherapy in patients with cervical carcinoma.

Desynchronous learning in a physics-driven learning network.

In a neuron network, synapses update individually using local information, allowing for entirely decentralized learning. In contrast, elements in an artificial neural network are typically updated simultaneously using a central processor. Here, we investigate the feasibility and effect of desynchronous learning in a recently introduced decentralized, physics-driven learning network. We show that desynchronizing the learning process does not degrade the performance for a variety of tasks in an idealized simulation. In experiment, desynchronization actually improves the performance by allowing the system to better explore the discretized state space of solutions. We draw an analogy between desynchronization and mini-batching in stochastic gradient descent and show that they have similar effects on the learning process. Desynchronizing the learning process establishes physics-driven learning networks as truly fully distributed learning machines, promoting better performance and scalability in deployment.

[Clinicopathological features of malignant mixed mesodermal tumor: analysis of 50 cases].

Objective: To investigate the clinicpathological, immunohistochemical and molecular genetic features of malignant mixed mesodermal tumor (MMMT) in the female reproductive system. Methods: To analyze its histopathological characteristics, we performed a retrospective review of the MMMT cases diagnosed at PLA General Hospital, Beijing, China during 2005-2019 using its surgical and pathological databases. EnVision immunohistochemical staining was used to detect the expression of ER, PR, p16, p53 and MMR proteins. Results: Fifty cases were conformed to the diagnosis, including 29 cases originated in the uterus, 16 cases in ovary, 4 cases of synchronous occurrence in uterus and ovary, 1 case in cervix. The tumor was histologically composed of two components, namely carcinoma and sarcoma ones, with clear borderline or blend mutually. The proportion of cancer component in the whole tumor ranged from 5%-90%. The proportion of carcinoma was more than 50% in 76% of the cases, and less than 50% in 24% of cases, including 2 cases with<10% of carcinoma. In the cases of primary uterine MMMT, the main carcinoma type was high grade endometrioid carcinoma (55%, 16/29). In ovarian MMMT, the main carcinoma type was serous carcinoma (12/16), while that of cervical MMMT was squamous cell carcinoma. The others were clear cell carcinoma or the undifferentiated carcinoma. There was one carcinoma type in most cases, only 7 cases had two carcinoma types. Homologous sarcomas, including stromal sarcoma, leiomyosarcoma and high-grade spindle cell sarcomas, were more commonly found in uterine MMMT (72.4%, 21/29). While heterogenic sarcomas, including chondrosarcoma, osteosarcoma and rhabdomyosarcoma, were more commonly noted in ovarian MMMT (12/16) than MMMT of other sites. There were 10 cases that consisted of two types of sarcomas. The synchronous MMMT of uterus and ovary had similar morphology and the types of carcinoma and sarcoma. The tumor cells that spread or metastasized to lymph node, omentum, intestinal wall or skin were all carcinoma cells, and were morphologically consistent with the original tumors. Immunohistochemically, ER and PR were both negative (23/25 in uterine, 8/10 in ovarian tumors). p16 was strongly positive (11/11 in uterine tumors, and 6/6 in ovarian tumors), with similar expression patterns in the carcinoma and sarcoma components. p53 showed mutant-type staining (64%, 21/33) and expressed synchronously in carcinoma and sarcoma components. p53 mutation was found in 35% cases of endometrial carcinoma and 46.7% cases of non-endometrial carcinoma. p53 mutation was also found in only 31.8% cases of heterogenic sarcomas, but in 50% of non-heterogenic sarcomas. Twenty-eight cases (28/33, 85%) presented intact mismatch repair proteins, while 5 cases (5/33, 15%) presented deficient mismatch repair proteins. Conclusions: MMMT in female reproductive system is a rare high-grade biphasic tumor with complex and diverse morphology. The immunohistochemical features are characterized by negative ER/PR and strongly positive p16, mostly mutant p53 and proficient mismatch repair proteins. The patients with a high FIGO stage have worse prognosis.

[Artificial intelligence aided measurement of cervical squamous epithelial thickness and its correlation with cervical precancerous lesions].

Objective: To study the thickness of cervical squamous epithelia and its correlation with cervical precancerous lesions. Methods: We selected 495 HE slides of 209 cervical biopsies from January 2020 to June 2020 in the Department of Pathology, the First and Seventh Medical Center of the PLA General Hospital, including 173 slides with low grade squamous intraepithelial lesion (LSIL) and 214 slides with high grade squamous intraepithelial lesion (HSIL). Artificial intelligence labeling software was used to assist in measuring the epithelial thickness of normal cervical squamous epithelium, LSIL and HSIL of each slide. The thickest, thinnest, and middle widths of epithelial thickness were measured, respectively. Average epithelial thickness was defined as the sum of the above three widths divided by 3. The correlation statistical analysis was performed by combining the data of age and pathological diagnosis. Results: The average thickness of normal cervical squamous mucosa was (245.83±91.40) µm, which was (222.42±81.22) µm and was (195.95±66.59) µm in LSIL and HISL epithelial respectively (F=27.09, P<0.01). The average cell layers of normal cervical squamous epithelium was (15.5±4.2) layers, which of LSIL was (14.8±4.8) layers, and that of HSIL was (15.8±4.8) layers. The differences among normal, LSIL and HSIL were not statistically significant (P>0.05). Further statistical analysis was stratified by age (≤30 years, 31-40 years, 41-50 years, 51-60 years, and >60 years), the results of Pearson correlation analysis showed that the thickness of normal cervical squamous epithelial gradually thinned with age (correlation coefficient r=-0.141 9, P<0.05), while LSIL and HSIL epithelial thickness had significant correlation with age (P>0.05). In the subgroup of ≤50 years old, the epithelial thickness of normal squamous epithelium was the thickest, followed by LSIL, and HSIL epithelial thickness was the thinnest. The differences were statistically significant (P<0.05). While in the subgroup of >50 years, the differences were not statistically significant (P>0.05). Conclusions: The cervical squamous epithelium gradually becomes thinner with the degree of precancerous lesions increasing among patients of ≤50 years old. However, after age of 50 years, with the onset of menopause, the normal mucosal epithelium is becoming atrophy, so that mucosal thickness is no longer correlated with the extent of the lesion. In addition, it is suggested that the cervical vinegar white test performance during colposcopy is related to the protein changes in the mucosal epithelial cells, but not directly related to the thickness of the epithelial layer.

[Comparison of the clinicopathological features between adenoid basal cell carcinoma and adenoid cystic carcinoma of the cervix].

Objective: To compare the clinical and histopathological characteristics of cervical adenoid basal cell carcinoma and adenoid cystic carcinoma for improving the diagnosis accuracy and differential diagnosis of these tumors. Methods: A retrospective study was conducted on 9 cases of cervical adenoid basal cell carcinoma and 3 cases of adenoid cystic carcinoma which were diagnosed and consulted at the First Medical Center of PLA General Hospital from March 2009 to April 2019. Detailed clinical data were reviewed. All pathological sections and immunohistochemical results were reviewed and the clinicopathological characteristics were analyzed. Follow-up information by telephone was collected and relevant literature was consulted. Results: Both tumors were more commonly found in postmenopausal women (the age of onset ranged 43-74 years). Adenoid basal cell carcinoma was often clinical asymptomatic. Most of them presented as abnormal smears of the cervix during physical examination, and there was no definite mass in colposcopy.Adenoid cystic carcinoma was mostly presented with abnormal vaginal bleeding. A mass was seen in colposcopy.Histologically, the two tumors were characterized by nest-like growth of the tumors, consisting of basal-like tumor cells, and often surrounded by palisade structures. The two lesions might coexist, or be mixed with squamous cell carcinoma or high-grade squamous intraepithelial lesions. The difference was that adenoid basal cell carcinoma was mostly located at the junction of cervical squamous epithelium and columnar epithelium and beneath the overlying epithelium, the tumor cells were arranged in nests, with squamous differentiation in the center of the nests, or in double-layer adenoid arrangement. The cell morphology was bland with occasional mitoses, and the stromal reaction was not obvious. And adenoid cystic carcinoma cells in the nest arranged like a sieve, the homogenous red-stained and blue-stained secretions were observed in the sieve holes, with obvious cell atypia, frequent mitoses, and obvious stromal reaction.In one case of adenoid cystic carcinoma, sarcomatoid area presented around the nests.Both of them were positive in clinical HPV test. Among the 9 cases of adenoid basal cell carcinoma, 3 were tested for HPV and 5 were tested for p16, and all showed positive expression. Among the 3 cases of adenoid cystic carcinoma, 2 were tested for HPV and 3 were tested for p16, both of which showed positive expression. Telephone follow-up was conducted by June 2019(follow-up time ranged 2-37 months). No recurrence or metastasis occurred in 7 of the 9 cases of adenoid basal cell carcinoma, while 1 case had a ground-glass nodule in lung and another had recurrence of vaginal stump 32 months after the surgery.One case of adenoid cystic carcinoma developed lung metastasis 8 months after surgery and died 2 years after surgery; another case was followed up for 6 months, which showed no recurrence or metastasis; the third case was lost to follow-up. Conclusions: Both adenoid cystic carcinoma and adenoid basal cell carcinoma of the cervix are the tumors originating from cervical reserve cells and are associated with high-risk HPV infection. Due to the differences in clinical treatment and prognosis, careful histological evaluation and immunohistochemical analysis should be carried out to make accurate pathological diagnosis.

[Expression of ARID1A in ovarian seromucinous neoplasms and its clinicopathological significance].

Objective: To investigate the clinical, pathological and immunohistochemical features of seromucinous neoplasms, including seromucinous cystadenoma, borderline tumour and seromucinous carcinomas of the ovary. Methods: A retrospective review of the seromucinous neoplasms collected between June 2006 and December 2018 was conducted at the First Medical Center of PLA General Hospital. EnVision immunohistochemical staining was used to detect the expression of CK7, PAX8, ER, PR, WT1, p16, p53 and Baf250a which was encoded by the ARID1A gene. Results: A total of 75 ovarian seromucinous neoplasms were included. There were 30 cases of benign seromucinous cystadenoma, whose patients aged 12 to 83 years (mean, 36 years). The tumor histologically composed of endocervical-type mucinous epithelium and serous-type cells, each of which accounted for more than 10%. Among the 34 cases of seromucinous borderline tumour including 7 cases with concurrent endometriosis, the patients aged 21 to 72 years (mean, 39 years). Characteristic histologic features were broad papilla structure and an admixture of cell types, predominant endocervical-like mucinous cells (non-intestinal, no goblet cells), eosinophilic cells and others such as clear cells, hobnail cells, ciliated cells, and endometrioid cells. The larger papillae tended to have oedematous stroma containing neutrophils. In the 11 cases of seromucinous carcinomas including 2 cases with concurrent endometriosis, patients aged 26 to 61 years (mean, 40 years). Seromucinous carcinomas exhibited a predominant papillary architecture with smaller components of confluent glandular, microglandular and solid structure, expansive stromal invasion pattern, and sometimes locally destructive infiltration. An admixture of epithelial cell types was in seromucinous carcinomas, as well as borderline tumour. Immunohistochemically, the tumours were positive for CK7, PAX8, p16, estrogen receptor and progesterone receptor (positive in 10% to 80% of the cases). They were negative for WT1, while p53 staining showed a "wild-type" pattern. The Ki-67 positive rate was 20% to 60%. Loss of ARID1A-encoded protein Baf250a staining was observed in 6 (30%) of the 20 seromucinous borderline tumors, and 2 of the 11 seromucinous carcinomas. According to FIGO 2014 staging system, there were 4 cases of ⅠA, 3 cases of ⅡA and 4 cases of ⅢC. Follow-up information was available in 9 patients of seromucinous carcinomas, and 2 lost to follow-up. Eight were alive (follow-up for 6 to 108 months), including 2 patients with relapse, but 1 patient who initially presented with a stage ⅢC tumor died of disease 60 months after the cancer diagnosis. Thirty-four patients of borderline tumour were all alive at the end of follow-up, including 1 with relapse. Conclusions: Seromucinous neoplasms have characteristic histopathological and immunopathological features. Both borderline tumors and carcinomas have complex structures and cellular components. ARID1A as a tumor-suppressor gene plays a role in the oncogenesis of ovarian seromucinous neoplasms. The loss of staining with ARID1A-encoded Baf250a and wild-type p53 in seromucinous neoplasms together support that seromucinous neoplasms could be type Ⅰ tumor of dualistic model of epithelial ovarian cancer, with favourable prognosis.

[A phenotypic and genetic study on ß-propeller protein-associated neurodegeneration].

Objective: To summarize the clinical and genetic features of ß-propeller protein-associated neurodegeneration (BPAN). Methods: The clinical data of 17 patients with BPAN with WDR45 gene variants were retrospectively collected at Children's Hospital of Fudan University, Peking University First Hospital, Capital Institute of Pediatrics, Shengjing Hospital of China Medical University and Shanghai Children's Hospital from June 2016 to December 2018, and their clinical manifestations, electroencephalogram, neuroimaging and genetics were analyzed. Results: Seventeen cases (13 females, 4 males), aged 1.1-8.8 years, were included. The median age of seizure onset was 14.5 months, from 3 months to 24 months of age, manifested with epileptic spasm in 6 cases and focal seizures in 5 cases. Eight patients had only one seizure type and 8 patients had two or more seizure types. Nine patients had complete remission of seizures. All 16 patients with seizures had developmental delay before the seizure onset, of whom 13 patients had moderate to severe seizures. The brain magnetic resonance imaging (MRI) was abnormal in 13 patients, including cerebral atrophy (10 cases) and thinning of the corpus callosum (9 cases). The brain magnetic susceptibility weighted imaging (SWI) in preschool stage showed prominent T2 hypointense signals in bilateral globus pallidus and brainstem ventral in two cases. Five seizure types (spasm, focal, absence, myodonic and generalized tonic clonic seizures)were found on ictal electroencephalogram(EEG) recordings. Compared to female patients(17(6-24) months of ege), male cases had earlier seizure onset (3, 4, 5, 18 months of age) . All patients had de novo variations in WDR45(6 nonsense, 4 frameshift, 3 missense and 4 splicing variations), with hemizygous variants in 3 males, mosaic variants in a male and heterozygous variants in 13 females, within which 5 variations had not been reported (c.977-1C>T,c.976+1G>C,c.10C>T,c.806del and c.110T>C). Conclusions: The patients with BPAN have profound developmental delay and are vulnerable to seizures. The male patients with BPAN tend to have more severer clinical phenotype than females. Early brain SWI could facilitate the timely diagnosis of this disease.

[Clinical characteristics of PCDH19-female limited epilepsy].

Objective: To analyze the clinical characteristics of patients with PCDH19-female limited epilepsy (PCDH19-FE). Methods: The clinical data of 60 female epilepsy patients with PCDH19 gene heterozygous variations at the Department of Pediatrics, Peking University First Hospital from October 2007 to December 2018 were collected and analyzed retrospectively, their clinical manifestations, accessory examination and follow-up treatment were summarized. Results: Data of a total of 60 cases of PCDH19-FE were collected. The seizure onset occurred between 4 and 42 months of age (median: 11 months of age). Focal seizures occurred in 47 patients (78%), generalized tonic-clonic seizures (GTCS) occurred in 30 patients (50%), and other rare types of seizures included atypical absence, myoclonic, clonic, tonic, and atonic seizures. Two or more seizures types existed in 24 patients (40%), and seven patients (12%) had attacks of status epilepticus. Sensitivity to fever was observed in 47 out of them (78%) and clustering of seizures as found in all patients. During the interictal phase, focal discharges were monitored in 22 cases (22/45, 49%), multifocal discharges in 12 cases (12/45, 27%), widely discharging in 2 cases (4%), and both focal and widely discharging in 9 cases (20%). Clinical seizures were detected in 30 patients during the electroencephalogram (EEG) recording, including focal seizures in 22 cases, GTCS seizures in 8 cases, tonic seizure in three cases, myoclonic seizure followed by GTCS in one case, and two types of seizures in four cases. Before seizure onset, 57 patients had normal development and three patients had delayed language development. After seizure onset, varied degrees of intelligence disability were present in 38 cases (63%), language delay in 36 cases (60%), and gait instability in 10 cases (17%). Autistic features occurred in 17 cases (28%); and other behavioral problems like learning difficulties, personality, or emotional disorders existed in 33 cases (55%). Age at last follow-up ranged from one year and 3 months to 22 years and 3 months of age, 17 patients (28%) were seizure-free for more than 2 years (5 to 22 years at the last follow-up). The efficiency of antiepileptic drugs were 65% (33/51) in sodium valproate, 63% (27/43) in levetiracetam and 59% (20/34) in topiramate. Conclusions: The clinical features of PCDH19-FE are characterized by clustering of seizures, focal seizures in most cases, sensitivity to fever mostly, focal discharges principally in EEG, varied degrees of intellectual disability or movement disorder, combined with autism spectrum disorders in partial and high efficiency in sodium valproate or levetiracetam treatment.

Heterogeneous Activation, Local Structure, and Softness in Supercooled Colloidal Liquids.

We experimentally characterize heterogeneous nonexponential relaxation in bidisperse supercooled colloidal liquids utilizing a recent concept called "softness" [Phys. Rev. Lett. 114, 108001 (2015)PRLTAO0031-900710.1103/PhysRevLett.114.108001]. Particle trajectory and structure data enable classification of particles into subgroups with different local environments and propensities to hop. We determine residence times t_{R} between particle hops and show that t_{R} derived from particles in the same softness subgroup are exponentially distributed. Using the mean residence time t[over ¯]_{R} for each softness subgroup, and a Kramers' reaction rate model, we estimate the activation energy barriers E_{b} for particle hops, and show that both t[over ¯]_{R} and E_{b} are monotonic functions of softness. Finally, we derive information about the combinations of large and small particle neighbors that determine particle softness, and we explicitly show that multiple exponential relaxation channels in the supercooled liquid give rise to its nonexponential behavior.

[Clinicopathological analysis of cervical basaloid squamous cell carcinoma].

Objective: To investigate the clinical and histopathological features of cervical basal squamous cell carcinoma (BSCC). Methods: A retrospective analysis of 10 cases of cervical BSCC was carried out. The clinical data and all the pathological sections were reviewed, the related immunohistochemical results were statistically analyzed, the clinicopathological features were analyzed, and then followed the prognosis. Results: (1) Clinical features: the median onset age of BSCC in cervix was 51 years old (ranged 35-69 years old), 5 of them were postmenopausal women. Vaginal bleeding was often seen in clinic (7 cases). Of the 10 cervical BSCC patients, 5 tested HPV types. All of them were HPV positive, including 2 cases of HPV 16 positive and 1 case of high-risk HPV positive. At the time of colposcopy, 3 cases showed exogenous nodular mass, 3 cases showed endogenous infiltrating mass, and 4 cases had unclear type of mass.(2)Treatment: of the 10 patients, 8 underwent hysterectomy+bilateral adnexal excision+pelvic lymphadenectomy, of which 6 underwent radiotherapy or chemotherapy after operation.Radiotherapy and chemotherapy were performed only in 2 cases. (3) Pathological features: histologically, the tumor cells were nests and stripe like growth, which were composed of basal like tumor cells. The cells had obvious heteromorphosis, less cytoplasm, deep dyed nuclei and common nuclear mitosis, and there were often palisade like structures around the cell nests, and some cells in the center of the cell nests were found to have acne like necrosis. It could be mixed with normal squamous cell carcinoma and squamous epithelial lesion. Among the 10 patients, 6 had immunohistochemical results. BSCC mainly expressed p16 and squamous cell markers such as p63, cytokeratin (CK) 5/6 and p40 protein, the positive expression rates were 3/3, 3/3, 2/2 and 3/3, respectively. A few expressed CK7 protein, and the positive expression rate was 1/3. (4) Prognosis: follow-up time ranged from 1 week to 64 months, and 2 cases were lost to follow-up. Among the 8 follow-up patients, 3 had iliac bone, lung or skin metastasis, and 5 had no recurrence or metastasis during the follow-up period. Conclusions: BSCC of cervix is a rare malignant tumor of cervix associated with high-risk HPV infection, p16 is more positive. The treatment is similar to that of normal cervical squamous cell carcinoma. Surgical resection and radiotherapy and chemotherapy are the most effective methods according to the clinical stage. At present, the disease is considered to be highly aggressive and the poor prognosis.